Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.94648536
The results demonstrate that MCH binds to the monkey MCH R 1 receptor with a K ( d ) of 6 . 5 nM and monkey MCH R 2 with a K ( d ) of 2 . 2 nM similar to K ( d ) values for human MCH R 1 and MCH R 2 . 0.94648536^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.53532401
The convergence of the orphan G protein coupled receptor SLC 1 with its orexigenic neuropeptide ligand melanin concentrating hormone ( MCH ) in 1999 stimulated considerable research activity aimed at characterizing the role of this receptor system in the regulation of body weight . 0.53532401^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Here we show that the 353 amino acid human orphan G protein coupled receptor SLC 1 expressed in HEK 293 cells binds MCH with sub nanomolar affinity , and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin elevated cyclic AMP levels . ^^^ We also show that SLC 1 messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei of the hypothalamus , consistent with a role for SLC 1 in mediating the effects of MCH on feeding . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
We demonstrate that nanomolar concentrations of MCH strongly activate SLC 1 related pathways through G ( alpha ) 1 and / or G ( alpha ) q proteins . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) , which is an orexigenic peptide , was isolated and identified as the endogenous ligand of the SLC 1 receptor . ^^^ Using HPLC purification , we isolated and identified MCH as the endogenous ligand of the SLC 1 receptor . ^^^ The authentic MCH demonstrated a dose dependent inhibitory effect on cAMP accumulation in forskolin stimulated rat and human SLC 1 expressing CHO cells with an EC ( 50 ) value of 0 . 2 nM for both the rat and human SLC 1 receptors . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Identification of melanin concentrating hormone ( MCH ) as the natural ligand for the orphan somatostatin like receptor 1 ( SLC 1 ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Here we identify MCH as the ligand for the orphan receptor SLC 1 . ^^^ The rat SLC 1 is activated by nanomolar concentrations of MCH and is coupled to the G protein G alpha i / o . ^^^ The pattern of SLC 1 messenger RNA expression coincides with the distribution of MCH containing nerve terminals and is consistent with the known central effects of MCH . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The distribution of the mRNA and protein products of the melanin concentrating hormone ( MCH ) receptor gene , slc 1 , in the central nervous system of the rat . ^^^ We recently identified the orphan G protein coupled receptor SLC 1 as a receptor for the neuropeptide MCH . ^^^ Our data are consistent with the known biological effects of MCH in the brain , e . g . modulation of the stress response , sexual behaviour , anxiety , learning , seizure production , grooming and sensory gating , and with a role for SLC 1 in mediating these physiological actions . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In addition , we demonstrate that the MCH receptor SLC 1 is expressed in adipocytes , suggesting that fat cells may be targets of MCH or an MCH like peptide under physiological conditions . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Recently , an orphan G protein coupled receptor ( SLC 1 ) was identified that binds MCH with high affinity . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Recently , using functional assays , the MCH receptor has been characterized as a seven transmembrane G coupled protein initially identified as SLC 1 . ^^^ We conclude that cells previously reported to express the MCH receptor do not express SLC 1 and that both iodinated MCH and the [ Phe ( 13 ) , Tyr ( 19 ) ] MCH have a large component of non specific binding . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The receptor for melanin concentrating hormone ( MCH ) was recently identified as the orphan G protein coupled receptor SLC 1 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
An orphan G protein coupled receptor ( SLC 1 / GPR24 ) has recently been identified as a receptor for MCH ( MCHR 1 ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Recently an orphan receptor , SLC 1 , has been identified as an MCH receptor ( MCH R 1 ) . ^^^ The pharmacological profile for mammalian MCH , [ Phe ( 13 ) , Tyr ( 19 ) ] MCH , and salmon MCH at MCH R 2 differed compared with MCH R 1 as assessed by intracellular signaling and radioligand binding assays . ^^^ By comparison , the EC ( 50 ) and IC ( 50 ) values of salmon MCH and mammalian MCH at MCH R 1 were relatively similar . ^^^ The receptor is composed of 340 amino acids encoded by a 1023 base pair cDNA and is 35 % homologous to SLC 1 . ( 125 ) 1 MCH specifically bound to Chinese hamster ovary cells stably expressing MCH R 2 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In this experiment , we measured the expressions of MCH as well as of its receptor ( SLC 1 ) in the hypothalamus of obese hyperphagic and lean Zucker rats by quantitative real time RT PCR . ^^^ MCH mRNA expression in the obese rats was significantly increased by a factor of five ( P < 0 . 01 ) whereas expression of SLC 1 was decreased by more than 50 % ( P < 0 . 05 ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
This receptor , named S643b , displays the greatest overall identity ( 32 % ) with the previously reported human SLC 1 receptor ( MCH 1 ) and to a lesser extent with the somatostatin receptor subtypes . ^^^ Comparative pharmacological studies using CHO cells stably expressing either SLC 1 or S643b receptors demonstrated that similar structural features of MCH are required to stimulate intracellular Ca ( 2+ ) mobilization at both receptors . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The orphan G protein coupled receptors SLC 1 and MCHR 2 were recently found to bind MCH with high affinity . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The MCH 1 receptor ( MCH1R ) is one of two recently identified G protein coupled receptors believed to be responsible for the actions of MCH . ^^^ Importantly , chronic central infusions of MCH induce hyperphagia and mild obesity in wild type mice , but not in Mch1r / mice . ^^^ We conclude that MCH1R is a physiologically relevant MCH receptor in mice that plays a role in energy homeostasis through multiple actions on locomotor activity , metabolism , appetite , and neuroendocrine function . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Recently the orphan G protein coupled receptor SLC 1 was identified as the MCH receptor ( MCHR ) . ^^^ Preliminary analyses of MCHR mRNA distribution have supported a role for the MCH system in nutritional homeostasis . ^^^ In most regions there was a good correspondence between MCHR mRNA distribution and that of MCH immunoreactive fibers . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Two MCH receptors ( MCHR 1 and MCHR 2 ) have been identified so far . ^^^ To decipher the functional role of the MCH receptors , we have generated and phenotypically characterized mice rendered deficient in MCHR 1 expression by homologous recombination . ^^^ Our data firmly establish MCHR 1 as a mediator of MCH effects on energy homeostasis and suggest that inactivation of MCHR 1 alone is capable to counterbalance obesity induced by a high fat diet . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
MCH signals in the brain occur via two seven transmembrane G protein coupled receptors , namely MCH 1 ( SLC 1 , MCH ( 1 ) , MCH R 1 , or MCH 1R ) and MCH 2 ( SLT , MCH ( 2 ) , MCH R 2 , or MCH 2R ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Recently , we reported that the orexigenic neuropeptide melanin concentrating hormone ( MCH ) stimulates leptin production by rat adipocytes and that the MCH receptor ( MCH R 1 ) is present on these cells . ^^^ Here , we show that MCH R 1 is present on murine 3T3 L 1 adipocytes . ^^^ Treatment of 3T3 L 1 adipocytes with 1 micromolar MCH for up to 2 h acutely downregulated MCH R 1 , indicating a mechanism of ligand induced receptor downregulation . ^^^ Potential signaling pathways mediating MCH R 1 action in adipocytes were investigated . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In this study , we have demonstrated the presence of melanin concentrating hormone ( MCH ) and melanin concentrating hormone receptor ( MCHR 1 ) transcripts in human skin . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
T 226296 exhibited high affinity for cloned human and rat MCH receptors ( SLC 1 ) in receptor binding assays ( IC50=5 . 5+ / 0 . 12 nM for human SLC 1 ; 8 . 6+ / 0 . 32 nM for rat SLC 1 ) . ^^^ In Chinese hamster ovary ( CHO ) cells expressing human SLC 1 , T 226296 reversed the MCH mediated inhibition of forskolin stimulated cAMP accumulation , inhibited MCH induced intracellular Ca2+ increase , and also inhibited MCH stimulated arachidonic acid release . ^^^ These results clearly indicate that T 226296 is a novel , orally active and selective MCH receptor antagonist that will be promising for further exploring the physiology and pathophysiology of MCH SLC 1 signaling . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) , a conserved cyclic neuropeptide implicated in the modulation of food intake , has been shown to bind and activate two G protein coupled receptors , called GPR 24 and MCHR 2 , expressed in human brain and other tissues . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Additionally , MCH was found to increase corticotropin releasing factor ( CRF ) release from hypothalamic explants , and this effect was abolished by the specific SLC 1 antagonist SB 568849 . ^^^ These results suggest that MCH has a stimulatory role in the HPA axis via SLC 1 , and that MCH exerts its effects predominantly through the PVN CRF neuronal populations . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Using the yeast two hybrid system a novel protein was identified from human brain that interacts with the C terminus of melanin concentrating hormone receptor 1 ( MCH R 1 ) . ^^^ This protein , characterized by a Myeloid translocation protein 8 , Nervy , DEAF 1 proteins ( MYND ) zinc finger domain , is termed MCH R 1 interacting zinc finger protein , MIZIP . ^^^ MIZIP is expressed in brain , testis and stomach , where expression of MCH and MCH R 1 was previously reported . ^^^ MIZIP interaction with MCH R 1 was verified by overlay and pull down assays as well as by co transfection experiments in human embryonic kidney 293 cells . ^^^ MIZIP is cytoplasmically localized but gets recruited to the plasma membrane when cells are co transfected with MCH R 1 supporting the notion that MIZIP is involved in the function of MCH R1 . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
RT PCR analysis revealed a low expression of prepro MCH and MCH receptor 1 ( MCHR 1 ) but not of MCHR 2 transcript in tissular and peripheral blood immune cells . ^^^ FACS and in vitro assay studies demonstrated that MCHR 1 receptor expression on most cell types can trigger , in the presence of MCH , cAMP synthesis and calcium mobilization in peripheral blood mononuclear cells ( PBMCs ) . ^^^ Accordingly , our data indicate for the first time that MCH and MCHR 1 may exert immunomodulatory functions . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Two receptor subtypes for MCH , MCH R 1 and MCH R 2 , have been cloned , but other receptor subtypes are likely to exist . ^^^ Summarizing all data currently available , we conclude that the two cloned MCH receptors , MCH R 1 and MCH R 2 , exhibit differences in their expression pattern , although MCH R 1 is generally colocalized in all tissues where MCH R 2 expression is found . ^^^ It appears that MCH R 1 is more abundant and has a wider distribution pattern than MCH R 2 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) is known to act through two G protein coupled receptors MCHR 1 and MCHR 2 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The importance of melanin concentrating hormone ( MCH ) in the control of energy balance has been confirmed by findings of lean phenotypes of mice with targeted deletion of the melanin concentrating hormone receptor 1 ( MCH 1 R ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Different structural requirements for melanin concentrating hormone ( MCH ) interacting with rat MCH R 1 ( SLC 1 ) and mouse B 16 cell MCH R . ^^^ Whereas the two MCH receptor subtypes hitherto cloned , MCH R 1 and MCH R 2 , are thought to mediate mainly the central effects of MCH , the MCH R on pigment cells has not yet been identified , although in some studies MCH R 1 was reported to be expressed by human melanocytes and melanoma cells . ^^^ Here we present data of a structure activity study in which 12 MCH peptides were tested on rat MCH R 1 and mouse B 16 melanoma cell MCH R , by comparing receptor binding affinities and biological activities . ^^^ For receptor binding analysis with HEK 293 cells expressing rat MCH R 1 ( SLC 1 ) , the radioligand was [ 125I ] [ Tyr 13 ] MCH with the natural sequence . ^^^ The bioassay used for MCH R 1 was intracellular Ca2+ mobilization quantified with the FLIPR instrument , whereas for B 16 MCH R the signal determined was MAP kinase activation . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
MCH receptor 1 ( MCHR 1 ) is the sole receptor expressed in rodents and couples to G ( 1 ) and G ( q ) proteins . ^^^ Using HEK 293 cells stably expressing MCHR 1 , we demonstrate that MCH , acting through MCHR 1 , antagonizes the action of forskolin , an adenylate cyclase activator that increases intracellular levels of cAMP . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Two receptors for MCH in humans have very recently been characterised , namely , MCH R 1 and MCH R 2 . ^^^ MCH R 1 has received considerable attention , as potent and selective antagonists acting at that receptor display anxiolytic , antidepressant and / or anorectic properties . ^^^ Thus , the discovery of MCH R 1 antagonists may lead to the development of valuable drugs to treat obesity , anxiety and depressive syndromes . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Ablation of the prepro MCH gene leads to a lean phenotype , as does ablation of the rodent MCH receptor , MCHR 1 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
To identify the hypothalamic nuclei responsible for the orexigenic effect , we injected the peptide into discrete hypothalamic nuclei known to express the MCH receptor , MCH1R . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
We investigated the use of Eu3+ chelate labeled analogues of melanin concentrating hormone ( MCH ) as ligands for both human MCH receptors ( MCHR 1 and MCHR 2 ) . ^^^ Both labeled Ala 17 MCH and S 36057 had high affinity for MCHR 1 ( Kd = 0 . 37 and 0 . 059nM , respectively ) while Eu3+ labeled S 36057 and R2P had high affinity for MCHR 2 ( Kd = 0 . 16 and 0 . 10nM , respectively ) . ^^^ Labeled Ala 17 MCH had little demonstrable binding affinity for MCHR 2 . ^^^ Competition binding experiments with both MCHR isoforms , a series of previously characterized alanine scan MCH analogues , and a recently identified nonpeptide MCHR 1 selective antagonist T 226296 confirmed the expected receptor selectivity . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Two MCH receptor subtypes , MCH R 1 and MCH R 2 , have been cloned which signal through activation of Gi / o / q proteins and hence regulate different intracellular signals , such as inhibition of cAMP formation , stimulation of IP 3 production , increase in intracellular free Ca2+ and / or activation of MAP kinases . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
By using HEK293T cells stably transfected with Flag tagged rat MCH1R , we investigated the mechanism underlying the MCH induced internalization pathway , which is important for the desensitization or regulation of the receptor response . ^^^ Overexpression of dominant negative beta arrestin 2 ( 284 409 ) or dynamin 1 K44A significantly prevented MCH induced internalization of MCH1R , while overexpression of dominant negative beta arrestin 1 V53D had no effect . ^^^ Our data suggest that MCH1R undergoes rapid MCH induced internalization through a PKC , beta arrestin 2 and dynamin 1 dependent pathway and that a portion of the C terminal tail plays an important role in the internalization process . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The current studies were carried out on a new line of mice lacking the rodent MCH receptor ( MCHR 1 ( / ) mice ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Identification and characterization of single nucleotide polymorphisms in MCH R 1 and MCH R 2 . ^^^ RESEARCH METHODS AND PROCEDURES : The entire coding regions and intron / exon splice junction regions of MCH R 1 and MCH R 2 were sequenced from anonymous white ( n=45 ) and African American ( n=46 ) individuals . ^^^ DNA constructs containing MCH R 1 and MCH R 2 SNPs were generated and expressed in CHO cells . ^^^ The effect of the SNPs in MCH R 1 and MCH R 2 were assessed in receptor binding assays and functional assays measuring changes in intracellular cAMP and Ca2+ levels . ^^^ RESULTS : We identified 12 SNPs in the MCH R 1 gene . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
We used real time PCR to measure the hypothalamic expression of MCH and its receptor ( MCHR 1 ) in two contrasting models of altered nutritional status , namely , obesity induced by 8 weeks ' voluntary overeating and food restriction for 10 days . ^^^ There were significant positive correlations ( p < 0 . 05 ) between plasma leptin concentration and both MCH and MCHR 1 mRNA levels , and between plasma insulin and MCHR 1 expression . ^^^ A positive correlation was also observed between MCH and MCHR 1 mRNA levels ( p < 0 . 05 ) . ^^^ Food restricted rats showed no significant alterations in the levels of either MCH mRNA or MCHR 1 mRNA . ^^^ The possibility that MCH and MCHR 1 expression are positively regulated by leptin and insulin , which normally inhibit feeding , is a putative explanation for how appetite for palatable food is able to override mechanisms that prevent the development of obesity . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) is a cyclic peptide that mediates its effects by the activation of two G protein coupled seven transmembrane receptors ( MCHR 1 and MCHR 2 ) in humans . ^^^ Chronic infusion or transgenic expression of MCH stimulates feeding and increases adipocity , whereas targeted deletion of MCH or its receptor ( MCHR 1 ) leads to resistance to diet induced obesity with increased energy expenditure and thermogenesis . ^^^ The involvement of MCH in energy homeostasis and in brain activity has also been validated in mice treated with non peptide antagonists , suggesting that blockade of MCHR 1 could provide a viable approach for treatment of obesity and certain neurological disorders . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In the present study , ghrelin was administered centrally to MCH receptor knockout ( MCHr KO ) mice . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) exerts a positive regulation on appetite and binds to the G protein coupled receptors , MCH1R and MCH2R . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) neurons and MCH 1 receptors ( MCH1r ) densely populate mesolimbic dopaminergic brain regions such as the nucleus accumbens ( NAc ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Here , we report in vitro and in vivo profiles of ATC 0065 [ N ( 2 ) [ cis 4 ( { 2 [ 4 bromo 2 ( trifluoromethoxy ) phenyl ] ethyl } amino ) cyclohexyl ] N ( 4 ) , N ( 4 ) dimethylquinazoline 2 , 4 diamine dihydrochloride ] and ATC 0175 [ N ( cis 4 { [ 4 ( dimethylamino ) quinazolin 2 yl ] amino } cyclohexyl ) 3 , 4 difluorobenzamide hydrochloride ] , newly synthesized MCH receptor 1 ( MCHR 1 ) antagonists . ^^^ Both ATC 0065 ( IC ( 50 ) = 21 . 4 + / 1 . 57 nM ) and ATC 0175 ( IC ( 50 ) = 13 . 5 + / 0 . 78 nM ) showed potent antagonist activities at MCHR 1 , as assessed by MCH increased guanosine 5 ' O ( 3 [ ( 35 ) S ] thio ) phosphate ( [ ( 35 ) S ] GTPgammaS ) binding to human MCHR 1 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The rodent MCH receptor ( MCH1R ) is highly expressed in the nucleus accumbens shell ( AcSh ) , a region that is important in the regulation of appetitive behavior . ^^^ Here we establish a role for MCH and MCH1R in mediating a hypothalamic limbic circuit that regulates feeding and related behaviors . ^^^ Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant like effect in the forced swim test , whereas intra AcSh injection of MCH had the opposite effect . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Antagonists of the MCH receptor are expected to affect food intake and weight gain , making MCH R 1 an attractive target for obesity treatment . ^^^ Herein , we report the discovery of a novel , orally active series of MCH R 1 antagonists that exhibit in vivo efficacy in rodent obesity models . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In addition , the MCH receptor ( MCHR 1 ) was coexpressed on about 50 55 % of GnRH neurons . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Significant correlation was observed between the sucrose intake and the mRNA expression of MCH and MCHR 1 in normal rats . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) receptor 1 ( MCH1R ) is a class A G protein coupled receptor . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In order to investigate the physiological properties of the melanin concentrating hormone ( MCH ) we have generated and used mice from which the MCH receptor 1 gene was deleted ( MCHR 1 ( Neo / Neo ) mice ) . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
We analysed the human MCH receptor 1 gene ( MCHR 1 ) with respect to human obesity . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
These data support the notion that MIZIP might interact with MCHR 1 in a cell type specific manner in vivo , suggesting a role in the regulation of MCH signalling in distinct regions of the mammalian brain . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Discovery and SAR of 4 amino 2 biarylbutylurea MCH 1 receptor antagonists through solid phase parallel synthesis . 4 Amino 2 arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor ( MCH1R ) antagonists via screening using a scintillation proximity assay based on [ 125I ] MCH binding to recombinant , human MCH1R . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The biological effects of the melanin concentrating hormone ( MCH ) are mediated by the melanin concentrating hormone receptor 1 ( MCHR 1 ) in mice . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The role of MCHR 1 in neuroendocrine , behavioral , and neurochemical stress , and anxiety related responses was examined by monitoring the effects of melanin concentrating hormone ( MCH ) and the selective MCHR 1 antagonist , GW 3430 , in inbred C57Bl / 6NTac and MCHR 1 knockout ( KO ) and wild type ( WT ) mice . ^^^ The selective MCHR 1 antagonist , GW 3430 , blocked the neuroendocrine and behavioral effects of MCH and produced anxiolytic like effects by itself in animal models of anxiety . ^^^ We show that MCH elicits anxiety like responses and that the effects of a selective MCHR 1 antagonist and the phenotype of KO mice are consistent with anxiolytic like action . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
To elucidate the physiological role of MCH in obesity development , the present study examined the effect of a selective MCH 1 receptor ( MCH1R ) antagonist in the diet induced obesity mouse model . ^^^ The MCH1R antagonist has high affinity and selectivity for MCH 1R and potently inhibits intracerebroventricularly injected MCH induced food intake in Sprague Dawley rats . ^^^ These results indicate that MCH has a major role in the development of diet induced obesity in mice and that a MCH1R antagonist might be a useful candidate as an antiobesity agent . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Many single digit nanomolar MCH R 1 antagonists have been identified from this series . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Novel benzimidazole analogues with increased chemical stability , devoid of the potential carcinogenic liability associated with a biarylamine moiety , were synthesized and evaluated to be potent MCH R 1 antagonists . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The G protein coupled receptor 24 encoded by GPR 24 binds melanin concentrating hormone ( MCH ) and has been implicated with feeding behavior , energy metabolism , and regulation of stress and mood . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
SAR of biphenyl carboxamide ligands of the human melanin concentrating hormone receptor 1 ( MCH R 1 ) : discovery of antagonist SB 568849 . ^^^ We report here the discovery of a class of MCH R 1 ligands based on a biphenyl carboxamide template . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Discovery of potent and stable conformationally constrained analogues of the MCH R 1 antagonist SB 568849 . ^^^ A strategy of systematically targeting more rigid analogues of the known MCH R 1 receptor antagonist , SB 568849 , serendipitously uncovered a binding mode accessible to N aryl phthalimide ligands . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
In this study , mice lacking both the MCH receptor 1 ( MCHr 1 knockout ) and leptin ( ob / ob ) double null mice ( MCHr 1 knockout ob / ob ) were generated to investigate whether the obesity and / or the insulin resistance linked to the obese phenotype of ob / ob mice was attenuated by ablation of the MCHr 1 gene . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) , an orexigenic neuropeptide in mammals , activates a G protein coupled receptor , MCHR 1 . ^^^ IMR 32 , a human neuroblastoma cell line , has been shown to express MCHR 1 mRNA ; however , we were unable to detect either MCH binding or MCH stimulated Ca++ mobilization in these cells . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The actions of MCH are , so far , known to be transduced through two seven transmembrane like receptor paralogues , named MCH1R and MCH2R . ^^^ MCH1R is an important receptor involved in mediating feeding behaviour modulation by MCH in rodents . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The MCH 1 receptor ( MCH R 1 ) has been identified as a key target in MCH regulation , as small molecule antagonists of MCH R 1 have demonstrated activity in vivo . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
We found that MCH receptor 1 ( MCH R 1 ) , but not MCH receptor 2 , is expressed in both normal ( fetal and adult ) human pituitary tissues and in GH cell adenomas . ^^^ Treatment of cultured GH adenoma cells with MCH ( 100 nM ) induced extracellular signal regulated kinases 1 and 2 phosphorylation , suggesting activation of MCH R 1 . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
To date , two receptor subtypes of MCH ( MCH1R and MCH2R ) have been identified . ^^^ MCH1R has been suggested to mediate most of the physiological functions of MCH . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Conversely , the conformationally constrained thienopyrimidinone analogs ( 18a g ) showed improved activity in MCH 1R and selectivity over 5HT2C . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The discovery and optimization of pyrimidinone containing MCH R 1 antagonists . ^^^ Optimization of a series of constrained melanin concentrating hormone receptor 1 ( MCH R 1 ) antagonists has provided compounds with potent and selective MCH R 1 activity . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
The action of MCH on feeding is thought to involve the activation of its respective G protein coupled receptor MCH R 1 . ^^^ Consequently , antagonists that block MCH regulated MCH R 1 activity may provide a viable approach to the treatment of diet induced obesity . ^^^ This communication reports the discovery of a novel MCH R 1 receptor antagonist , the biarylether 7 , identified through high throughput screening . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Novel benzimidazole based MCH R 1 antagonists . ^^^ The identification of an MCH R 1 antagonist screening hit led to the optimization of a class of benzimidazole based MCH R 1 antagonists . ^^^ Structure activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R 1 antagonist in an animal model of obesity . . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Since its discovery as the first receptor for the orexigenic neuropeptide melanin concentrating hormone ( MCH ) , the MCH receptor , MCHR 1 , has been actively pursued for therapeutic intervention in the treatment of obesity . ^^^ Mice with targeted deletion of MCHR 1 or its cognate ligand , MCH , generally have decreased body weight and fat mass and are resistant to diet induced obesity compared with their wild type counterparts . ^^^ Mice treated via intracerebroventricular infusion with MCH , or that overexpress MCH or MCHR 1 , exhibit weight gain compared with control animals . ^^^ The distribution of MCH and MCHR 1 in rat brain , outside of regions that control appetite and satiety , has led to the finding that MCH signaling participates in other functions such as emotion and stress . ^^^ This review will describe in detail the biological studies that show how MCH and MCHR 1 control numerous physiological functions . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
Enhanced running wheel activity of both Mch1r and Pmch deficient mice . ^^^
Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: P20382 and Q99705	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.94648536
The results demonstrate that MCH binds to the monkey MCH R 1 receptor with a K ( d ) of 6 . 5 nM and monkey MCH R 2 with a K ( d ) of 2 . 2 nM similar to K ( d ) values for human MCH R 1 and MCH R 2 . 0.94648536^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.53532401
The convergence of the orphan G protein coupled receptor SLC 1 with its orexigenic neuropeptide ligand melanin concentrating hormone ( MCH ) in 1999 stimulated considerable research activity aimed at characterizing the role of this receptor system in the regulation of body weight . 0.53532401^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The G protein coupled receptor 24 encoded by GPR 24 binds melanin concentrating hormone ( MCH ) and has been implicated with feeding behavior , energy metabolism , and regulation of stress and mood . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The MCH 1 receptor ( MCH1R ) is one of two recently identified G protein coupled receptors believed to be responsible for the actions of MCH . ^^^ Importantly , chronic central infusions of MCH induce hyperphagia and mild obesity in wild type mice , but not in Mch1r / mice . ^^^ We conclude that MCH1R is a physiologically relevant MCH receptor in mice that plays a role in energy homeostasis through multiple actions on locomotor activity , metabolism , appetite , and neuroendocrine function . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
MCH signals in the brain occur via two seven transmembrane G protein coupled receptors , namely MCH 1 ( SLC 1 , MCH ( 1 ) , MCH R 1 , or MCH 1R ) and MCH 2 ( SLT , MCH ( 2 ) , MCH R 2 , or MCH 2R ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
To identify the hypothalamic nuclei responsible for the orexigenic effect , we injected the peptide into discrete hypothalamic nuclei known to express the MCH receptor , MCH1R . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
By using HEK293T cells stably transfected with Flag tagged rat MCH1R , we investigated the mechanism underlying the MCH induced internalization pathway , which is important for the desensitization or regulation of the receptor response . ^^^ Overexpression of dominant negative beta arrestin 2 ( 284 409 ) or dynamin 1 K44A significantly prevented MCH induced internalization of MCH1R , while overexpression of dominant negative beta arrestin 1 V53D had no effect . ^^^ Our data suggest that MCH1R undergoes rapid MCH induced internalization through a PKC , beta arrestin 2 and dynamin 1 dependent pathway and that a portion of the C terminal tail plays an important role in the internalization process . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Enhanced running wheel activity of both Mch1r and Pmch deficient mice . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) exerts a positive regulation on appetite and binds to the G protein coupled receptors , MCH1R and MCH2R . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) neurons and MCH 1 receptors ( MCH1r ) densely populate mesolimbic dopaminergic brain regions such as the nucleus accumbens ( NAc ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The rodent MCH receptor ( MCH1R ) is highly expressed in the nucleus accumbens shell ( AcSh ) , a region that is important in the regulation of appetitive behavior . ^^^ Here we establish a role for MCH and MCH1R in mediating a hypothalamic limbic circuit that regulates feeding and related behaviors . ^^^ Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant like effect in the forced swim test , whereas intra AcSh injection of MCH had the opposite effect . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
To elucidate the physiological role of MCH in obesity development , the present study examined the effect of a selective MCH 1 receptor ( MCH1R ) antagonist in the diet induced obesity mouse model . ^^^ The MCH1R antagonist has high affinity and selectivity for MCH 1R and potently inhibits intracerebroventricularly injected MCH induced food intake in Sprague Dawley rats . ^^^ These results indicate that MCH has a major role in the development of diet induced obesity in mice and that a MCH1R antagonist might be a useful candidate as an antiobesity agent . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) receptor 1 ( MCH1R ) is a class A G protein coupled receptor . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Discovery and SAR of 4 amino 2 biarylbutylurea MCH 1 receptor antagonists through solid phase parallel synthesis . 4 Amino 2 arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor ( MCH1R ) antagonists via screening using a scintillation proximity assay based on [ 125I ] MCH binding to recombinant , human MCH1R . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Conversely , the conformationally constrained thienopyrimidinone analogs ( 18a g ) showed improved activity in MCH 1R and selectivity over 5HT2C . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Recently the orphan G protein coupled receptor SLC 1 was identified as the MCH receptor ( MCHR ) . ^^^ Preliminary analyses of MCHR mRNA distribution have supported a role for the MCH system in nutritional homeostasis . ^^^ In most regions there was a good correspondence between MCHR mRNA distribution and that of MCH immunoreactive fibers . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
We investigated the use of Eu3+ chelate labeled analogues of melanin concentrating hormone ( MCH ) as ligands for both human MCH receptors ( MCHR 1 and MCHR 2 ) . ^^^ Both labeled Ala 17 MCH and S 36057 had high affinity for MCHR 1 ( Kd = 0 . 37 and 0 . 059nM , respectively ) while Eu3+ labeled S 36057 and R2P had high affinity for MCHR 2 ( Kd = 0 . 16 and 0 . 10nM , respectively ) . ^^^ Labeled Ala 17 MCH had little demonstrable binding affinity for MCHR 2 . ^^^ Competition binding experiments with both MCHR isoforms , a series of previously characterized alanine scan MCH analogues , and a recently identified nonpeptide MCHR 1 selective antagonist T 226296 confirmed the expected receptor selectivity . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In the present study , ghrelin was administered centrally to MCH receptor knockout ( MCHr KO ) mice . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
An orphan G protein coupled receptor ( SLC 1 / GPR24 ) has recently been identified as a receptor for MCH ( MCHR 1 ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Recently an orphan receptor , SLC 1 , has been identified as an MCH receptor ( MCH R 1 ) . ^^^ The pharmacological profile for mammalian MCH , [ Phe ( 13 ) , Tyr ( 19 ) ] MCH , and salmon MCH at MCH R 2 differed compared with MCH R 1 as assessed by intracellular signaling and radioligand binding assays . ^^^ By comparison , the EC ( 50 ) and IC ( 50 ) values of salmon MCH and mammalian MCH at MCH R 1 were relatively similar . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The actions of MCH are , so far , known to be transduced through two seven transmembrane like receptor paralogues , named MCH1R and MCH2R . ^^^ MCH1R is an important receptor involved in mediating feeding behaviour modulation by MCH in rodents . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
To date , two receptor subtypes of MCH ( MCH1R and MCH2R ) have been identified . ^^^ MCH1R has been suggested to mediate most of the physiological functions of MCH . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Two MCH receptors ( MCHR 1 and MCHR 2 ) have been identified so far . ^^^ To decipher the functional role of the MCH receptors , we have generated and phenotypically characterized mice rendered deficient in MCHR 1 expression by homologous recombination . ^^^ Our data firmly establish MCHR 1 as a mediator of MCH effects on energy homeostasis and suggest that inactivation of MCHR 1 alone is capable to counterbalance obesity induced by a high fat diet . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Recently , we reported that the orexigenic neuropeptide melanin concentrating hormone ( MCH ) stimulates leptin production by rat adipocytes and that the MCH receptor ( MCH R 1 ) is present on these cells . ^^^ Here , we show that MCH R 1 is present on murine 3T3 L 1 adipocytes . ^^^ Treatment of 3T3 L 1 adipocytes with 1 micromolar MCH for up to 2 h acutely downregulated MCH R 1 , indicating a mechanism of ligand induced receptor downregulation . ^^^ Potential signaling pathways mediating MCH R 1 action in adipocytes were investigated . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In this study , we have demonstrated the presence of melanin concentrating hormone ( MCH ) and melanin concentrating hormone receptor ( MCHR 1 ) transcripts in human skin . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Using the yeast two hybrid system a novel protein was identified from human brain that interacts with the C terminus of melanin concentrating hormone receptor 1 ( MCH R 1 ) . ^^^ This protein , characterized by a Myeloid translocation protein 8 , Nervy , DEAF 1 proteins ( MYND ) zinc finger domain , is termed MCH R 1 interacting zinc finger protein , MIZIP . ^^^ MIZIP is expressed in brain , testis and stomach , where expression of MCH and MCH R 1 was previously reported . ^^^ MIZIP interaction with MCH R 1 was verified by overlay and pull down assays as well as by co transfection experiments in human embryonic kidney 293 cells . ^^^ MIZIP is cytoplasmically localized but gets recruited to the plasma membrane when cells are co transfected with MCH R 1 supporting the notion that MIZIP is involved in the function of MCH R1 . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
RT PCR analysis revealed a low expression of prepro MCH and MCH receptor 1 ( MCHR 1 ) but not of MCHR 2 transcript in tissular and peripheral blood immune cells . ^^^ FACS and in vitro assay studies demonstrated that MCHR 1 receptor expression on most cell types can trigger , in the presence of MCH , cAMP synthesis and calcium mobilization in peripheral blood mononuclear cells ( PBMCs ) . ^^^ Accordingly , our data indicate for the first time that MCH and MCHR 1 may exert immunomodulatory functions . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Two receptor subtypes for MCH , MCH R 1 and MCH R 2 , have been cloned , but other receptor subtypes are likely to exist . ^^^ Summarizing all data currently available , we conclude that the two cloned MCH receptors , MCH R 1 and MCH R 2 , exhibit differences in their expression pattern , although MCH R 1 is generally colocalized in all tissues where MCH R 2 expression is found . ^^^ It appears that MCH R 1 is more abundant and has a wider distribution pattern than MCH R 2 . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) is known to act through two G protein coupled receptors MCHR 1 and MCHR 2 . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Different structural requirements for melanin concentrating hormone ( MCH ) interacting with rat MCH R 1 ( SLC 1 ) and mouse B 16 cell MCH R . ^^^ Whereas the two MCH receptor subtypes hitherto cloned , MCH R 1 and MCH R 2 , are thought to mediate mainly the central effects of MCH , the MCH R on pigment cells has not yet been identified , although in some studies MCH R 1 was reported to be expressed by human melanocytes and melanoma cells . ^^^ Here we present data of a structure activity study in which 12 MCH peptides were tested on rat MCH R 1 and mouse B 16 melanoma cell MCH R , by comparing receptor binding affinities and biological activities . ^^^ For receptor binding analysis with HEK 293 cells expressing rat MCH R 1 ( SLC 1 ) , the radioligand was [ 125I ] [ Tyr 13 ] MCH with the natural sequence . ^^^ The bioassay used for MCH R 1 was intracellular Ca2+ mobilization quantified with the FLIPR instrument , whereas for B 16 MCH R the signal determined was MAP kinase activation . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
MCH receptor 1 ( MCHR 1 ) is the sole receptor expressed in rodents and couples to G ( 1 ) and G ( q ) proteins . ^^^ Using HEK 293 cells stably expressing MCHR 1 , we demonstrate that MCH , acting through MCHR 1 , antagonizes the action of forskolin , an adenylate cyclase activator that increases intracellular levels of cAMP . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Two receptors for MCH in humans have very recently been characterised , namely , MCH R 1 and MCH R 2 . ^^^ MCH R 1 has received considerable attention , as potent and selective antagonists acting at that receptor display anxiolytic , antidepressant and / or anorectic properties . ^^^ Thus , the discovery of MCH R 1 antagonists may lead to the development of valuable drugs to treat obesity , anxiety and depressive syndromes . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Ablation of the prepro MCH gene leads to a lean phenotype , as does ablation of the rodent MCH receptor , MCHR 1 . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The current studies were carried out on a new line of mice lacking the rodent MCH receptor ( MCHR 1 ( / ) mice ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Identification and characterization of single nucleotide polymorphisms in MCH R 1 and MCH R 2 . ^^^ RESEARCH METHODS AND PROCEDURES : The entire coding regions and intron / exon splice junction regions of MCH R 1 and MCH R 2 were sequenced from anonymous white ( n=45 ) and African American ( n=46 ) individuals . ^^^ DNA constructs containing MCH R 1 and MCH R 2 SNPs were generated and expressed in CHO cells . ^^^ The effect of the SNPs in MCH R 1 and MCH R 2 were assessed in receptor binding assays and functional assays measuring changes in intracellular cAMP and Ca2+ levels . ^^^ RESULTS : We identified 12 SNPs in the MCH R 1 gene . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
We used real time PCR to measure the hypothalamic expression of MCH and its receptor ( MCHR 1 ) in two contrasting models of altered nutritional status , namely , obesity induced by 8 weeks ' voluntary overeating and food restriction for 10 days . ^^^ There were significant positive correlations ( p < 0 . 05 ) between plasma leptin concentration and both MCH and MCHR 1 mRNA levels , and between plasma insulin and MCHR 1 expression . ^^^ A positive correlation was also observed between MCH and MCHR 1 mRNA levels ( p < 0 . 05 ) . ^^^ Food restricted rats showed no significant alterations in the levels of either MCH mRNA or MCHR 1 mRNA . ^^^ The possibility that MCH and MCHR 1 expression are positively regulated by leptin and insulin , which normally inhibit feeding , is a putative explanation for how appetite for palatable food is able to override mechanisms that prevent the development of obesity . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Two MCH receptor subtypes , MCH R 1 and MCH R 2 , have been cloned which signal through activation of Gi / o / q proteins and hence regulate different intracellular signals , such as inhibition of cAMP formation , stimulation of IP 3 production , increase in intracellular free Ca2+ and / or activation of MAP kinases . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) is a cyclic peptide that mediates its effects by the activation of two G protein coupled seven transmembrane receptors ( MCHR 1 and MCHR 2 ) in humans . ^^^ Chronic infusion or transgenic expression of MCH stimulates feeding and increases adipocity , whereas targeted deletion of MCH or its receptor ( MCHR 1 ) leads to resistance to diet induced obesity with increased energy expenditure and thermogenesis . ^^^ The involvement of MCH in energy homeostasis and in brain activity has also been validated in mice treated with non peptide antagonists , suggesting that blockade of MCHR 1 could provide a viable approach for treatment of obesity and certain neurological disorders . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Here , we report in vitro and in vivo profiles of ATC 0065 [ N ( 2 ) [ cis 4 ( { 2 [ 4 bromo 2 ( trifluoromethoxy ) phenyl ] ethyl } amino ) cyclohexyl ] N ( 4 ) , N ( 4 ) dimethylquinazoline 2 , 4 diamine dihydrochloride ] and ATC 0175 [ N ( cis 4 { [ 4 ( dimethylamino ) quinazolin 2 yl ] amino } cyclohexyl ) 3 , 4 difluorobenzamide hydrochloride ] , newly synthesized MCH receptor 1 ( MCHR 1 ) antagonists . ^^^ Both ATC 0065 ( IC ( 50 ) = 21 . 4 + / 1 . 57 nM ) and ATC 0175 ( IC ( 50 ) = 13 . 5 + / 0 . 78 nM ) showed potent antagonist activities at MCHR 1 , as assessed by MCH increased guanosine 5 ' O ( 3 [ ( 35 ) S ] thio ) phosphate ( [ ( 35 ) S ] GTPgammaS ) binding to human MCHR 1 . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Antagonists of the MCH receptor are expected to affect food intake and weight gain , making MCH R 1 an attractive target for obesity treatment . ^^^ Herein , we report the discovery of a novel , orally active series of MCH R 1 antagonists that exhibit in vivo efficacy in rodent obesity models . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In addition , the MCH receptor ( MCHR 1 ) was coexpressed on about 50 55 % of GnRH neurons . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Significant correlation was observed between the sucrose intake and the mRNA expression of MCH and MCHR 1 in normal rats . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In order to investigate the physiological properties of the melanin concentrating hormone ( MCH ) we have generated and used mice from which the MCH receptor 1 gene was deleted ( MCHR 1 ( Neo / Neo ) mice ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
We analysed the human MCH receptor 1 gene ( MCHR 1 ) with respect to human obesity . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
These data support the notion that MIZIP might interact with MCHR 1 in a cell type specific manner in vivo , suggesting a role in the regulation of MCH signalling in distinct regions of the mammalian brain . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The biological effects of the melanin concentrating hormone ( MCH ) are mediated by the melanin concentrating hormone receptor 1 ( MCHR 1 ) in mice . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The role of MCHR 1 in neuroendocrine , behavioral , and neurochemical stress , and anxiety related responses was examined by monitoring the effects of melanin concentrating hormone ( MCH ) and the selective MCHR 1 antagonist , GW 3430 , in inbred C57Bl / 6NTac and MCHR 1 knockout ( KO ) and wild type ( WT ) mice . ^^^ The selective MCHR 1 antagonist , GW 3430 , blocked the neuroendocrine and behavioral effects of MCH and produced anxiolytic like effects by itself in animal models of anxiety . ^^^ We show that MCH elicits anxiety like responses and that the effects of a selective MCHR 1 antagonist and the phenotype of KO mice are consistent with anxiolytic like action . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In this study , mice lacking both the MCH receptor 1 ( MCHr 1 knockout ) and leptin ( ob / ob ) double null mice ( MCHr 1 knockout ob / ob ) were generated to investigate whether the obesity and / or the insulin resistance linked to the obese phenotype of ob / ob mice was attenuated by ablation of the MCHr 1 gene . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The MCH 1 receptor ( MCH R 1 ) has been identified as a key target in MCH regulation , as small molecule antagonists of MCH R 1 have demonstrated activity in vivo . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
We found that MCH receptor 1 ( MCH R 1 ) , but not MCH receptor 2 , is expressed in both normal ( fetal and adult ) human pituitary tissues and in GH cell adenomas . ^^^ Treatment of cultured GH adenoma cells with MCH ( 100 nM ) induced extracellular signal regulated kinases 1 and 2 phosphorylation , suggesting activation of MCH R 1 . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Many single digit nanomolar MCH R 1 antagonists have been identified from this series . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Novel benzimidazole analogues with increased chemical stability , devoid of the potential carcinogenic liability associated with a biarylamine moiety , were synthesized and evaluated to be potent MCH R 1 antagonists . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
SAR of biphenyl carboxamide ligands of the human melanin concentrating hormone receptor 1 ( MCH R 1 ) : discovery of antagonist SB 568849 . ^^^ We report here the discovery of a class of MCH R 1 ligands based on a biphenyl carboxamide template . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Discovery of potent and stable conformationally constrained analogues of the MCH R 1 antagonist SB 568849 . ^^^ A strategy of systematically targeting more rigid analogues of the known MCH R 1 receptor antagonist , SB 568849 , serendipitously uncovered a binding mode accessible to N aryl phthalimide ligands . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The discovery and optimization of pyrimidinone containing MCH R 1 antagonists . ^^^ Optimization of a series of constrained melanin concentrating hormone receptor 1 ( MCH R 1 ) antagonists has provided compounds with potent and selective MCH R 1 activity . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The action of MCH on feeding is thought to involve the activation of its respective G protein coupled receptor MCH R 1 . ^^^ Consequently , antagonists that block MCH regulated MCH R 1 activity may provide a viable approach to the treatment of diet induced obesity . ^^^ This communication reports the discovery of a novel MCH R 1 receptor antagonist , the biarylether 7 , identified through high throughput screening . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) , an orexigenic neuropeptide in mammals , activates a G protein coupled receptor , MCHR 1 . ^^^ IMR 32 , a human neuroblastoma cell line , has been shown to express MCHR 1 mRNA ; however , we were unable to detect either MCH binding or MCH stimulated Ca++ mobilization in these cells . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Since its discovery as the first receptor for the orexigenic neuropeptide melanin concentrating hormone ( MCH ) , the MCH receptor , MCHR 1 , has been actively pursued for therapeutic intervention in the treatment of obesity . ^^^ Mice with targeted deletion of MCHR 1 or its cognate ligand , MCH , generally have decreased body weight and fat mass and are resistant to diet induced obesity compared with their wild type counterparts . ^^^ Mice treated via intracerebroventricular infusion with MCH , or that overexpress MCH or MCHR 1 , exhibit weight gain compared with control animals . ^^^ The distribution of MCH and MCHR 1 in rat brain , outside of regions that control appetite and satiety , has led to the finding that MCH signaling participates in other functions such as emotion and stress . ^^^ This review will describe in detail the biological studies that show how MCH and MCHR 1 control numerous physiological functions . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The importance of melanin concentrating hormone ( MCH ) in the control of energy balance has been confirmed by findings of lean phenotypes of mice with targeted deletion of the melanin concentrating hormone receptor 1 ( MCH 1 R ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Here we show that the 353 amino acid human orphan G protein coupled receptor SLC 1 expressed in HEK 293 cells binds MCH with sub nanomolar affinity , and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin elevated cyclic AMP levels . ^^^ We also show that SLC 1 messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei of the hypothalamus , consistent with a role for SLC 1 in mediating the effects of MCH on feeding . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
We demonstrate that nanomolar concentrations of MCH strongly activate SLC 1 related pathways through G ( alpha ) 1 and / or G ( alpha ) q proteins . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) , which is an orexigenic peptide , was isolated and identified as the endogenous ligand of the SLC 1 receptor . ^^^ Using HPLC purification , we isolated and identified MCH as the endogenous ligand of the SLC 1 receptor . ^^^ The authentic MCH demonstrated a dose dependent inhibitory effect on cAMP accumulation in forskolin stimulated rat and human SLC 1 expressing CHO cells with an EC ( 50 ) value of 0 . 2 nM for both the rat and human SLC 1 receptors . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Identification of melanin concentrating hormone ( MCH ) as the natural ligand for the orphan somatostatin like receptor 1 ( SLC 1 ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Novel benzimidazole based MCH R 1 antagonists . ^^^ The identification of an MCH R 1 antagonist screening hit led to the optimization of a class of benzimidazole based MCH R 1 antagonists . ^^^ Structure activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R 1 antagonist in an animal model of obesity . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Recently , an orphan G protein coupled receptor ( SLC 1 ) was identified that binds MCH with high affinity . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Recently , using functional assays , the MCH receptor has been characterized as a seven transmembrane G coupled protein initially identified as SLC 1 . ^^^ We conclude that cells previously reported to express the MCH receptor do not express SLC 1 and that both iodinated MCH and the [ Phe ( 13 ) , Tyr ( 19 ) ] MCH have a large component of non specific binding . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The receptor for melanin concentrating hormone ( MCH ) was recently identified as the orphan G protein coupled receptor SLC 1 . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In this experiment , we measured the expressions of MCH as well as of its receptor ( SLC 1 ) in the hypothalamus of obese hyperphagic and lean Zucker rats by quantitative real time RT PCR . ^^^ MCH mRNA expression in the obese rats was significantly increased by a factor of five ( P < 0 . 01 ) whereas expression of SLC 1 was decreased by more than 50 % ( P < 0 . 05 ) . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
This receptor , named S643b , displays the greatest overall identity ( 32 % ) with the previously reported human SLC 1 receptor ( MCH 1 ) and to a lesser extent with the somatostatin receptor subtypes . ^^^ Comparative pharmacological studies using CHO cells stably expressing either SLC 1 or S643b receptors demonstrated that similar structural features of MCH are required to stimulate intracellular Ca ( 2+ ) mobilization at both receptors . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The orphan G protein coupled receptors SLC 1 and MCHR 2 were recently found to bind MCH with high affinity . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Here we identify MCH as the ligand for the orphan receptor SLC 1 . ^^^ The rat SLC 1 is activated by nanomolar concentrations of MCH and is coupled to the G protein G alpha i / o . ^^^ The pattern of SLC 1 messenger RNA expression coincides with the distribution of MCH containing nerve terminals and is consistent with the known central effects of MCH . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
The distribution of the mRNA and protein products of the melanin concentrating hormone ( MCH ) receptor gene , slc 1 , in the central nervous system of the rat . ^^^ We recently identified the orphan G protein coupled receptor SLC 1 as a receptor for the neuropeptide MCH . ^^^ Our data are consistent with the known biological effects of MCH in the brain , e . g . modulation of the stress response , sexual behaviour , anxiety , learning , seizure production , grooming and sensory gating , and with a role for SLC 1 in mediating these physiological actions . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
In addition , we demonstrate that the MCH receptor SLC 1 is expressed in adipocytes , suggesting that fat cells may be targets of MCH or an MCH like peptide under physiological conditions . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
T 226296 exhibited high affinity for cloned human and rat MCH receptors ( SLC 1 ) in receptor binding assays ( IC50=5 . 5+ / 0 . 12 nM for human SLC 1 ; 8 . 6+ / 0 . 32 nM for rat SLC 1 ) . ^^^ In Chinese hamster ovary ( CHO ) cells expressing human SLC 1 , T 226296 reversed the MCH mediated inhibition of forskolin stimulated cAMP accumulation , inhibited MCH induced intracellular Ca2+ increase , and also inhibited MCH stimulated arachidonic acid release . ^^^ These results clearly indicate that T 226296 is a novel , orally active and selective MCH receptor antagonist that will be promising for further exploring the physiology and pathophysiology of MCH SLC 1 signaling . . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Additionally , MCH was found to increase corticotropin releasing factor ( CRF ) release from hypothalamic explants , and this effect was abolished by the specific SLC 1 antagonist SB 568849 . ^^^ These results suggest that MCH has a stimulatory role in the HPA axis via SLC 1 , and that MCH exerts its effects predominantly through the PVN CRF neuronal populations . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
Melanin concentrating hormone ( MCH ) , a conserved cyclic neuropeptide implicated in the modulation of food intake , has been shown to bind and activate two G protein coupled receptors , called GPR 24 and MCHR 2 , expressed in human brain and other tissues . ^^^
Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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Interacting proteins: Q99705 and P20382	Pubmed	SVM Score :0.0
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