| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.91478804 |
| To better understand the interplay between the AGRP and melanocortin signaling systems , we compared their nerve fiber distributions with each other by immunohistochemistry and their perikarya distribution with MC3R and MC4R by double in situ hybridization . 0.91478804^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| However the effect of exogenous Agrp and its in vivo interaction with alpha melanocyte stimulating hormone ( alphaMSH ) , the likely endogenous melanocortin 3 and 4 receptor ( MC 3 R and MC 4 R ) agonist , have not been demonstrated . ^^^ We have also shown Agrp ( 83 132 ) is an antagonist at the MC 3 R and MC 4 R , with similar inhibition of cAMP activation to that previously reported for the full length peptide . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| In both conventional and photoemulsion binding studies [ 125I ] AGRP ( 87 132 ) was observed only to bind to cells expressing melanocortin receptors MC3R , MC4R , and MC5R . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| AGRP containing neurons are not visualized in a number of areas , including portions of the amygdala , thalamus , and brain stem , that express MC 3 R and MC 4 R messenger RNA and receive innervation from POMC neurons that serve as the source of melanocortin agonists . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The present studies were designed to examine the contribution of extracytoplasmic domains of the melanocortin 4 receptor ( MC4R ) to AGRP binding by making chimerical receptor constructs of the human melanocortin 1 receptor ( MC1R ; a receptor that is not inhibited by AGRP ) and the human MC4R ( a receptor that is potently inhibited by AGRP ) . ^^^ Substitutions of the extracytoplasmic NH 2 terminus and the first extracytoplasmic loop ( exoloop ) of the MC4R with homologous domains of the MC1R had no effect on AGRP ( 87 132 ) binding affinity or inhibitory activity ( the ability to inhibit melanocortin stimulated cAMP generation ) . ^^^ In contrast , cassette substitutions of exoloops 2 and 3 of the MC4R with the homologous exoloops of the MC1R resulted in a substantial loss of AGRP binding affinity and inhibitory activity . ^^^ Conversely , the exchange of exoloops 2 and 3 of the MC1R with the homologous exoloops of the MC4R was found to confer AGRP binding and inhibitory activity to the basic structure of the MC1R . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Melanocortin 4 receptor ( MC 4 R ) density is thought to be regulated by synaptic availability of endogenous agonist , alpha melanocyte stimulating hormone ( alpha MSH ) , and also by agouti related protein ( AGRP ) , which acts as a competitive antagonist . ^^^ As hypothalamic MC 4 R have been implicated in the regulation of energy balance , we examined concentrations of alpha MSH and AGRP in hypothalami of dietary obese and food restricted rats . ^^^ In conclusion , we suggest that MC 4 R activity may not be regulated by changes in agonist ( alpha MSH ) but by changes in the antagonist ( AGRP ) availability , which may modulate background activation of the receptor by tonic alpha MSH release . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Recently , two potential downstream mediators , agouti related protein ( Agrp ) and its receptor , the melanocortin 4 receptor ( Mc4r ) , have been identified . ^^^ Agrp and Mc4r are excellent candidates for human disorders of body weight regulation and represent promising targets for pharmacological intervention in the treatment of these disorders . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| While AGRP ' s exact mechanism of action is unknown , it has been identified as a competitive antagonist of melanocortin receptors 3 and 4 ( MC3r , MC4r ) , and MC4r in particular is implicated in the hypothalamic control of feeding behavior . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| It has been shown to be expressed in mice hypothalamus and to act similarly to agouti as a potent antagonist to central melanocortin receptor MC 4 R , suggesting that AGRP is an endogenous MC 4 R ligand . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Moreover , the effects of AgRP are not limited to its actions at the melanocortin 4 receptor ( MC4R ) , because MC4R deficient ( MC4R / ) mice manifest a significant response to centrally administered AgRP . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( Agrp ) ( 83 132 ) , a biologically active fragment of the endogenous MC 4 R antagonist , administered ICV at a dose of 1 nmol completely blocked the anorectic effect of 1 nmol alpha MSH . ^^^ Thus , as previous data suggests , GLP 1 and CRF do not appear to reduce food intake predominantly via MC 4 R , we here demonstrate for the first time that CART , in addition to GLP 1 and CRF primarily acts via Agrp independent pathways . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| We investigated which hypothalamic areas known to express MC4R are involved in the regulation of feeding by using alpha melanocyte stimulating hormone ( alpha MSH ) , an endogenous MC4R agonist , and agouti related peptide ( Agrp ) , an endogenous MC4R antagonist . ^^^ This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha MSH with regard to their effect on feeding . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( AGRP ) is a naturally occurring antagonist of the brain melanocortin receptors ( MC3R and MC4R ) and is physiologically implicated as participating in feeding behavior and energy homeostasis . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| By integrating an agonist satiety signal , provided by alpha melanocyte stimulating hormone ( alpha MSH ) , and an antagonist signal , provided by agouti related protein ( AGRP ) , the melanocortin 4 receptor ( MC 4 R ) is a key element in the hypothalamic control of food intake . ^^^ This variable expressivity of MC 4 R associated obesity is not due to variations in genes for alpha MSH or AGRP . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Conversely , MC 4 R antagonists such as ' agouti ' protein and agouti gene related peptide ( AGRP ) stimulate feeding and cause obesity . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The system comprises alpha MSH , which acts as agonist , and agouti related protein ( AgRP ) , which acts as antagonist at the MC 3 and MC 4 receptors ( MC3R and MC4R ) . ^^^ The effect of AgRP ( 83 132 ) on the hMC4R was blocked by the MC4R ligand SHU 9119 . ^^^ These findings form a basis to further investigate the relevance of constitutive activity of the MC4R and of inverse agonism of AgRP for the regulation of body weight . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| AGRP has been identified in vitro , as competitively antagonizing the brain melanocortin 4 ( MC4R ) and melanocortin 3 ( MC3R ) receptors , and when over expressed in transgenic mice , results in an obese phenotype . ^^^ AGRP possesses inverse agonist activity at this constitutively active MC4R . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti protein and agouti related protein ( AGRP ) antagonize alpha melanocyte stimulating hormone that binds to and activates the melanocortin 4 receptor ( MC 4 R ) in the hypothalamus , thereby stimulating food intake . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related peptide ( AgRP ) , a homologue of agouti peptide and antagonist of MC3R and MC4R , is expressed in human brain and may act as a inhibitor of alpha MSH . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The anorexigenic effect of alpha MSH is attenuated by agouti related protein ( AGRP ) , an antagonist for MC4R . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : To search for mutations in melanocortin pathway elements , that is , the melanocortin 4 receptor ( MC4R ) , agouti related protein ( AGRP ) , and ( alpha melanocyte stimulating hormone ( alpha MSH ) genes in children with severe obesity . ^^^ STUDY DESIGN : Direct sequencing of the MC4R encoding sequence and single strand polymorphism conformation analysis of AGRP and alpha MSH genes were performed in 63 severely obese children . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| High affinity binding sites were demonstrated in the GT 1 1 and GT 1 7 cells for NDP alpha melanocyte stimulating hormone ( MSH ; K ( 1 ) = 1 . 1 10 10 ( 10 ) and 1 . 8 10 10 ( 10 ) M ) and agouti related protein ( AGRP ; K ( 1 ) = 1 . 548 10 10 ( 9 ) and 1 . 663 ( 9 ) M ) . alpha MSH stimulated cAMP production in GT 1 1 cells with an EC ( 50 ) of 2 . 2 10 10 ( 8 ) M , and cAMP production was inhibited in the presence of AGRP , an endogenous antagonist of the MC 4 R . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The agouti related protein ( AGRP ) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic ( appetite stimulating ) activity . ^^^ Consideration of these sequence differences , along with recent experiments on mutant and chimeric melanocortin receptors , allows us to postulate that this loop in the first 16 residues of its C terminal domain confers AGRP ' s distinct selectivity for MC3R and MC4R . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Activation of MC 4 R , possibly mediated by blockade of AGRP release , appears to restrain overeating of a palatable diet . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| AgRP ( 83 132 ) , a nonselective MC3 / 4 R antagonist , induced no change in TRH release whilst JKC 363 ( cyclic [ Mpr 11 , D Nal 14 , Cys 18 , Asp 22 NH2 ] beta MSH 11 22 ) , a selective MC 4 R antagonist , suppressed it ( JKC 363 10 nm 57 . 2 + / 11 . 5 % basal , P < 0 . 05 ) . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The prolonged food intake stimulation does not seem to depend on continued competition at the melanocortin 4 receptor ( MC4R ) , because the relatively specific MC4R agonist MTII regains its ability to suppress food intake 24 h after AgRP injection . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The agouti related protein ( AGRP ) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic activity . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| AgRP is believed to exert its effects through the blockade of signaling by alpha melanocyte stimulating hormone at central nervous system ( CNS ) melanocortin 3 receptor ( Mc3r ) and Mc4r . ^^^ In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin , Mc3r , Mc4r , or NPY mRNAs in Agrp ( / ) mice . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Examination of this DNal ( 2 ' ) containing tetrapeptide at the F254S and F259S mutant mMC4Rs resulted in agonist activity of this mMC4R tetrapeptide antagonist , similar to that observed for the SHU 9119 peptide , supporting our previously proposed hypothesis that the Phe 254 and 259 transmembrane six receptor residues are important for differentiating melanocortin sequence based MC4R antagonists vs the agouti related protein ( AGRP ) sequence based antagonists . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The central melanocortinergic system consists of endogenous agonist alpha melanocyte stimulating hormone , the naturally occurring antagonist Agouti related protein ( AGRP ) , and two melanocortin receptors ( MC3R , MC4R ) . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( AGRP ) is an endogenous antagonist of the melanocortin action . ( 1 ) In the hypothalamus , melanocortin peptide agonists act as satiety inducing factors that mediate their action through the melanocortin 4 receptor ( MC4R ) whereas AGRP is an opposing orexigenic agent . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Work from our laboratory and others over the last several years has demonstrated that the non pigmentary effects of A ( y ) are caused by ectopic expression of Agouti protein , a paracrine signaling molecule whose normal function is to inhibit signaling through the melanocortin 1 receptor ( Mc1r ) , but which can mimic the effects of Agouti related protein ( Agrp ) , a homologous neuropeptide produced in the medial portion of the arcuate nucleus that acts as a potent antagonist of the Mc3r and Mc4r . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The melanocortin 4 receptor ( MC 4 R ) is an important mediator of the effects of two melanocortin system ligands , alpha melanocyte stimulating hormone ( alpha MSH ) and agouti related peptide ( AGRP ) , on feeding behavior and energy balance in mammals . ^^^ Food deprived doves showed a fourfold increase in the number of AGRP immunoreactive cells in the tuberal region of the hypothalamus and 5 ng of the MC 3 R and MC 4 R agonist MTII significantly attenuated the amount of food consumed by food deprived birds that were allowed to re feed . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( AgRP ) an endogenous antagonist at the MC 3 R and MC 4 R , is expressed in the adrenal gland . ^^^ We investigated the expression of the MC 3 R and MC 4 R and the role of AgRP in the adrenal gland . ^^^ AgRP acting via the MC 3 R or MC 4 R may have an inhibitory paracrine role , blocking alpha MSH induced corticosterone secretion . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| To clarify the roles of the MC 3 R and MC 4 R in AgRP induced hyperphagia , the feeding effect of AgRP ( 83 132 ) was compared with that of the selective MC 4 R antagonist , JKC 363 ( cyclic [ Mpr 11 , D Nal 14 , Cys 18 , Asp 22 NH2 ] beta MSH 11 22 ) . ^^^ These data suggest that the sustained orexigenic action of AgRP ( 83 132 ) may not be through MC 4 R antagonism . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Two melanocortin receptors ( MC3R , MC4R ) are expressed in brain regions receiving projections of POMC fibers , most of which also receive projections from a population of ARC neurons that co express neuropeptide Y ( NPY ) and the MC3R / MC4R antagonist agouti related peptide ( AgRP ) . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The agouti related protein ( AGRP ) is an endogenous antagonist of the brain melanocortin receptors ( MC3R and MC4R ) and is believed to be involved in feeding behavior and energy homeostasis . ^^^ Previous results identified that the human AGRP decapeptide Yc [ CRFFNAFC ] Y binds to the MC3R and MC4R and acts as an antagonist at the MC4R but not at the MC3R . ^^^ The binding IC ( 50 ) values of radiolabeled hAGRP ( 86 132 ) versus NDP MSH were identical within experimental error , supporting the hypothesis that AGRP and NDP MSH interact with overlapping binding epitopes at the MC3R and MC4R . ^^^ Interestingly , extension of the AGRP ( 109 118 ) decapeptide at both the N and C terminus by two amino acids conferred detectable mMC3R antagonism , while retaining high nanomolar MC4R antagonist and micromolar MC1R agonist pharmacological properties . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( AGRP ) is an endogenous antagonist of the melanocortin 4 receptor ( MC4R ) that functions in the hypothalamic control of feeding behavior . ^^^ Our previous studies have suggested that in addition to exoloops 2 and 3 , several transmembrane domains of MC4R may be important for AGRP binding . ^^^ However , the detailed molecular basis of MC4R domains in AGRP binding is presently unclear . ^^^ The present studies were designed to determine the specific contribution of MC4R exoloops and transmembrane domains to AGRP binding by using chimeric receptor constructs of the human melanocortin 1 receptor ( hMC1R ) , a receptor that is not inhibited by AGRP , and the human MC4R ( hMC4R ) , a receptor that is potently inhibited by AGRP . ^^^ Our results indicate that substitutions of the second and third extracellular loops of the MC4R with homologous domains of the MC1R dramatically decreased AGRP 87 132 binding affinity , but did not affect AGRP 110 117 binding affinity . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| We examined hypothalamic gene expressions of Ob Rb , NPY , AgRP , POMC , MC 4 R , and preproorexins in pregnant Wistar rats at day 19 of gestation . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The agouti related protein ( AGRP ) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic activity . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| In young ( 35 to 56 day old ) and middle aged ( 9 mo old ) wild type ( + / + ) and melanocortin 4 receptor ( MC4R ) deficient ( + / , / ) mice , expressions of neuropeptide Y ( NPY ) , agouti related protein ( AGRP ) , pro opiomelanocortin ( POMC ) , and cocaine and amphetamine regulated transcript ( CART ) were analyzed in the arcuate nucleus ( ARC ) and adjacent regions comprising the dorsomedial ( DMN ) and ventromedial ( VMN ) nucleus . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Although mutations in the agouti gene cause an over expression of agouti peptide which antagonizes effects of alpha MSH at MC 4 R in the brain and causes obese phenotypes , there was no evidence for the presence of an endogenous antagonist for MC 3 R and MC 4 R until agouti related protein ( AGRP ) was identified . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( Agrp ) , primarily expressed in the hypothalamus , is an endogenous antagonist of alphaMSH at the level of melanocortin 3 receptor ( MC 3 R ) and MC 4 R , but the adrenal gland represents the second major Agrp expressing tissue . ^^^ In our studies , ( Nle 4 , d Phe 7 ) alphaMSH ( NDP alphaMSH ) stimulated the production of cortisol in a dose dependent manner , and these effects were abolished by Agrp or SHU 9119 , a synthetic antagonist of MC 3 R and MC 4 R . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Previous data showed that recombinant full length agouti and a synthetic fragment of AgRP , AgRP ( 83 132 ) , are inverse agonists at the MC1R and MC4R , respectively . ^^^ This study demonstrates the smaller analogs AgRP ( 87 120 ) and ASIP [ 90 132 ( L89Y ) ] , and short peptides Yc [ CRFFNAFC ] Y and Qc [ CRFFRSAC ] S are also MC4R inverse agonists . ^^^ Furthermore , the relative affinity of the series of MC4R ligands for displacement of radiolabeled antagonist 125I AgRP ( 86 132 ) versus radiolabeled agonist 125I NDP MSH did not correlate with ligand efficacy , which is more consistent with an induced fit model than a simple two state model of MC4R activation . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| We investigated if agouti related peptide ( AgRP ) , an endogenous antagonist of melanocortin receptors ( MC 3 R and MC 4 R ) , effects energy expenditure in rats . ^^^ Despite the absence of hyperphagia and cross reactivities with MC 4 R , AgRP ( 25 51 ) and AgRP ( 54 82 ) significantly increased body weight and epididymal / mesenteric fat weight . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The central melanocortin system consists of alpha MSH , agouti related protein ( AGRP ) , MC3R and MC4R . ^^^ AGRP and alpha MSH are believed to be the natural antagonist and agonist respectively of MC3R and MC4R . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Altered levels of POMC , AgRP and MC 4 R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high energy diet induced obesity . ^^^ This study has investigated the levels of mRNA expression of proopiomelanocortin ( POMC ) , agouti related protein ( AgRP ) and the melanocortin 4 receptor ( MC 4 R ) in diet induced obese ( DIO ) and diet resistant ( DR ) mice . ^^^ In conclusion , this study has demonstrated that differential expression of POMC , AgRP and MC 4 R mRNA levels exists in DIO , DR and LF mice . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Interactions between pro opiomelanocortin ( POMC ) derived peptides , agouti related protein ( AGRP ) and the melanocortin 4 receptor ( MC 4 R ) are central to energy homeostasis . ^^^ There was no significant difference in the potency of inhibition by AGRP ( 83 132 ) or agouti ( 87 132 ) at the MC 4 R , regardless of which POMC peptide was used as an agonist . ^^^ Furthermore , we have found that AGRP ( 83 132 ) has no effect on the dissociation kinetics of radiolabelled Nle 4 , D Phe 7 MSH from the MC 4 R , indicating an absence of allosteric effects . ^^^ This provides strong pharmacological evidence that AGRP ( 83 132 ) acts orthosterically at the MC 4 R to inhibit Gs coupled accumulation of intracellular cAMP . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Mice that are engineered to be deficient for the melanocortin 4 receptor ( MC4R ) or pro opiomelanocortin ( POMC ) and those that overexpress agouti or agouti related protein ( AgRP ) all have a characteristic obese phenotype typified by hyperphagia , increased linear growth , and metabolic defects . ^^^ The central melanocortin system modulates energy homeostasis through the actions of the agonist , alpha melanocyte stimulating hormone ( alpha MSH ) , a POMC cleavage product , and the endogenous antagonist AgRP on the MC3R and MC4R . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Leptin secretion ( measured by ELISA ) and gene expression ( by real time quantitative PCR ) of differentiated rat adipocytes cultured in vitro were inhibited by the administration of alpha MSH ( EC50=0 . 24 nM ) , and this effect was antagonised by antagonists of the melanocortin receptors MC4R and MC3R ( AgRP and SHU 9119 ) . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Insight into putative interactions between the antagonist AGRP amino acids with the melanocortin 4 receptor ( MC4R ) may be important for the design of unique ligands for the treatment of obesity related diseases and is currently lacking in the literature . ^^^ Key putative AGRP MC4R interactions include the Arg 111 of hAGRP ( 87 132 ) interacting in a negatively charged pocket located in a cavity formed by transmembrane spanning ( TM ) helices 1 , 2 , 3 , and 7 , capped by the acidic first extracellular loop ( EL 1 ) and specifically with the conserved melanocortin receptor residues mMC4R Glu 92 ( TM 2 ) , mMC4R Asp 114 ( TM 3 ) , and mMC4R Asp 118 ( TM 3 ) . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Leptin activates Arc neurons producing alpha melanocyte stimulating hormone ( alpha MSH ) and inhibits those producing agouti related protein ( AgRP ) . alpha MSH is an endogenous agonist for the melanocortin 4 receptor ( MC 4 R ) that is expressed exclusively in the central nervous system ( CNS ) , whereas AgRP acts as a MC 4 R antagonist . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The study shows that some parts of the MC system are highly conserved through vertebrate evolution , such as regions in POMC coding for ACTH , alpha MSH , and beta MSH , the C terminal region of AGRP , key binding units within the MC1R , MC2R , MC4R , and MC5R , synteny blocks around the MCRs , pharmacological properties of the MC2R , whereas other parts in the system are either missing , such as the MC3R and gamma MSH , or different as compared to mammals , such as the affinity of ACTH and MSH peptides to MC1R and MC4R and the anatomical expression pattern of the MCRs . . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Food intake , energy expenditure , adiposity , BAT UCP 1 , and leptin expression in white fat as well as hypothalamic expressions of MC3R , MC4R , POMC , AgRP and NPY were assessed . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Thus , we determined whether the central effects of AGRP on the HPT axis are altered in mice with selective deletion of the melanocortin 4 receptor ( MC 4 R ) . ^^^ AGRP or artificial cerebrospinal fluid was administered daily into the lateral ventricle of adult , male MC 4 R knockout and wild type ( WT ) mice for 3 d . ^^^ In contrast , no significant effects of AGRP were observed in any of these parameters in the MC 4 R knockout mice . ^^^ These data suggest that AGRP signaling to TRH hypophysiotropic neurons in the paraventricular nucleus is primarily mediated by the MC 4 R and therefore , binding to the MC 3 R or other putative AGRP receptors may have only a minor role . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Control of MC4R activity in vivo is modulated by the opposing effects of the anorexigenic agonist alpha melanocyte stimulating hormone ( alpha MSH ) and the orexigenic antagonist agouti related protein ( AGRP ) . ^^^ In addition , experiments in vitro have demonstrated that the human MC4R has an intrinsic constitutive activity on which AGRP also acts as an inverse agonist . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| AGRP is synthesized in the brain and is an antagonist of the melanocortin 3 and 4 receptors ( MC3R , MC4R ) . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NDP alpha MSH induced a time dependent internalization of MC 4 R that was partially prevented by AgRP . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The agouti related protein ( AgRP ) exerts its anabolic effects on food intake by antagonising the alpha melanocyte stimulating hormone ( alpha MSH ) at its receptors , melanocortin receptors 3 and 4 ( MC3R and MC4R ) . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Here we describe treatment of Agrp ( / ) ; Npy ( / ) and Mc3r ( / ) ; Mc4r ( / ) double knockout mice as well as Npy ( / ) and Agrp ( / ) single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : A great deal of attention has focused on the central role of alpha melanocyte stimulating hormone ( alpha MSH ) and its antagonism at the melanocortin 4 receptor ( MC4R ) by agouti related protein ( AgRP ) in the regulation of energy balance . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( AgRP ( 83 132 ) ) , a known endogenous MC3R and MC4R antagonist , did not reduce the stimulation of prolactin mRNA expression by gamma 3 MSH or Ala ( 8 ) gamma 2 MSH . ^^^ AgRP appears to have other actions than its known antagonistic activity on the MC3R and MC4R . . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| We showed that Agrp inhibited , in a dose dependent manner , the 10 ( 9 ) M NDP alphaMSH induced cortisol production through its antagonistic properties towards MSH at the level of MC 4 R . ^^^ Our data confirmed that Agrp is not an antagonist of ACTH at the level of MC 2 R and that its sustained effect on ACTH induced steroidogenesis did not involve its antagonistic properties at the level of MC 4 R . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Additionally leptin inhibits release of agouti related protein ( AgRP ) , an MC4R antagonist . ^^^ |
|
| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| METHODS : We genotyped polymorphisms in the melanocortin 4 receptor ( MC4R ) , melanocortin 3 receptor ( MC3R ) , neuropeptide Y ( NPY ) , neuropeptide Y Y 1 receptor ( NPY Y1R ) , cocaine and amphetamine regulated transcript ( CART ) , agouti related protein ( AGRP ) , and pro opiomelanocortin ( POMC ) genes in 669 subjects ( age ( X+ / s . d . ) : parents : 52+ / 3 . 4 y ; offspring : 28+ / 8 . 7 y ) . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The hypothesis that the interaction of agouti related protein ( AGRP ) and the melanocortin 4 receptor ( MC4R ) modulates feeding behavior in humans has stimulated the synthesis of conformationally constrained peptides , peptoids and small molecules in efforts to identify novel compounds that can potentially be used in the clinical treatment of obesity and related eating disorders . ^^^ In addition , the availability of a high resolution NMR structure for the MC4R binding domain of AGRP , and studies employing site specific murine MC4R mutants have identified key intermolecular AGRP / MC4R interactions . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Administration of JKC 363 , a selective MC4R specific antagonist , coupled with [ Gln ( 6 ) ] alpha MSH ND , specifically reversed the [ Gln ( 6 ) ] alpha MSH ND induced inhibition of food intake , but also reversed the hypothalamic expression levels of neuropeptides such as AGRP , NPY , MCH , and POMC , which suggests [ Gln ( 6 ) ] alpha MSH ND can function as a selective MC4R agonist . . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Also , no differences were observed between the potencies of bacterially expressed Ala 67 and Thr 67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats . ^^^ Taken together , no evidence was found for a functional defect of Thr 67 AgRP related to MC4R interactions . . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Here we assessed the possibility that MC receptor ( MCR ) agonists modulate ethanol intake via the MC 3 receptor ( MC3R ) and / or the MC 4 receptor ( MC4R ) and whether the MCR antagonist AgRP ( 83 132 ) controls ethanol consumption . ^^^ Furthermore , ICV infusion of the MC4R agonist significantly reduced ethanol drinking , whereas ICV infusion of AgRP ( 83 132 ) significantly increased ethanol drinking in C57BL / 6J mice . ^^^ CONCLUSIONS : The present results suggest that MC4R , and not MC3R , modulates MCR agonist induced reduction of ethanol consumption and that ethanol intake is increased by the antagonistic actions of AgRP ( 83 132 ) . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| Agouti related protein ( AgRP ) is an endogenous antagonist at the MC 3 R and MC 4 R and is expressed in the rat adrenal cortex . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The carboxyl terminal domain of AGRP acts as an endogenous antagonist of the melanocortin 4 receptor ( MC 4 R ) . ^^^ It has been suggested that the amino terminal domain of AGRP binds to syndecan 3 , thereby modulating the effects of carboxyl terminal AGRP at the MC 4 R . ^^^ We also found that AGRP ( 83 132 ) is more potent an antagonist than full length AGRP , based on cAMP reporter assays , suggesting that posttranslational cleavage is required to potentiate the effect of AGRP at the MC 4 R . ^^^ Because AGRP is cleaved before secretion , syndecan 3 must influence food intake independently of the MC 4 R . . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| The endogenous MC4R antagonist , agouti related protein ( AGRP ) , is expressed in the brain and is only one of two naturally occurring antagonists of GPCRs identified to date . ^^^ |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O00253 and P32245 |
Pubmed |
SVM Score :0.0 |
| NA |
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