| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.50317413 |
| Preincubation of endothelin 1 with 1 microgram recombinant human NEP decreased the contractile activity of endothelin 1 by 72 + / 9 % , whereas no effect was observed using heat inactivated NEP . 0.50317413^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Effect of enkephalinase inhibitor on endothelin 1 induced bronchoconstriction in guinea pigs ] . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Thermolysin , a bacterial neutral endopeptidase with a similar substrate specificity to neutral endopeptidase 24 . 11 initially cleaves endothelin 1 between His 16 Leu17 which lies within the COOH terminal linear `` tail ' ' portion of the molecule . ^^^ The cleavage of endothelins 2 and 3 by neutral endopeptidase 24 . 11 differs from that observed with endothelin 1 in that cleavage of these endothelins occurs at Asp 18 Ile19 within the linear COOH terminal tail structure . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon caused progressive vasodilatation when infused alone , with blood flow increasing by 37 % at 90 min ( P = 0 . 02 ) , whereas thiorphan caused vasoconstriction , consistent with NEP inhibition exerting its major effect on degradation of constrictor peptides , such as angiotensin and endothelin 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| In vivo the effects of endothelin 1 ( ET 1 ) are limited by its rapid removal from the circulation and possibly by its metabolism by enzymes such as neutral endopeptidase 24 . 11 , deamidase or carboxypeptidase A . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The results are consistent with SQ 28 , 603 not only inhibiting NEP that is involved in the degradation of ANP , but also suppressing activity of the enzyme involved in the conversion of proendothelin 1 [ 1 38 ] to endothelin 1 . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| To study the role of neutral endopeptidase ( NEP ) on endothelin 1 induced contraction of the airway smooth muscle , we examined the contractile effect of endothelin 1 in the isolated guinea pig trachea and human bronchus in the presence or absence of NEP inhibitor phosphoramidon . ^^^ Because NEP is known to cleave tachykinins , we next studied whether endothelin 1 contracts airway tissues by releasing endogenous tachykinins from bronchial C fibers . ^^^ From these results , we conclude that NEP plays an important role in regulating endothelin 1 induced contraction in the guinea pig trachea and human bronchus . . ^^^ Neutral endopeptidase inhibitor potentiates endothelin 1 induced airway smooth muscle contraction . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| In the present study , we investigated the effects of CsA administration ( 50 mg / kg per day i . p . for 6 days ) to rats on plasma and urinary levels of endothelin ; expression of endothelin 1 ( ET 1 ) , ET 3 , and endothelin converting enzyme in renal tissue ; clearance of infused 125I ET 1 ; and degradation of 125I ET 1 by recombinant neutral endopeptidase . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endothelin 1 metabolism by neutral endopeptidase 24 . 11 identified in cultured human skeletal muscle myocytes and fibroblasts . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The inhibition by an ETA receptor antagonist and the restoration by a neutral endopeptidase ( NEP ) inhibitor of the second phase of bronchoconstriction suggests that primary activation of ETB receptors leads to autocrine / paracrine endothelin 1 ( ET 1 ) release that would subsequently cause profound bronchoconstriction through both ETA and ETB receptor activation . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Isolation and characterization of endothelin converting enzyme which cleaves big endothelin 1 , an intermediate form , into mature endothelin 1 has revealed a type 2 integral membrane bound metalloprotease that is structurally homologous to neutral endopeptidase . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| In this study , we used reverse transcriptase polymerase chain reaction ( RT PCR ) to compare the expression of mRNAs encoding endothelin 1 ( ET 1 ) , endothelin receptors type A ( ETA R ) and type B ( ETB R ) and ET 1 degrading enzyme neutral endopeptidase 24 . 11 ( NEP ) in 15 endometrial cancer tissues and 13 normal endometrial tissues . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Unlike CGS 24592 , a potent but selective NEP inhibitor , CGS 26303 significantly blocks endothelin 1 production in rats after exogenous administration of big ET 1 and reduces the mean arterial pressure in spontaneously hypertensive rats during chronic administration . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The expression of mRNAs encoding endothelin 1 ( ET 1 ) and its receptors ( ETA R and ETB R ) as well as the ET degrading enzyme , neutral endopeptidase 24 . 11 ( NEP ) , was determined in tissue samples of endometrium , myometrium and leiomyoma by using a reverse transcriptase polymerase chain reaction ( RT PCR ) technique . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibitors of neutral endopeptidase EC . 3 . 4 . 24 . 11 ( NEP ) have been shown to attenuate the hypertensive effect of big endothelin 1 ( BET 1 ) in rats . ^^^ To determine whether NEP converts BET 1 to endothelin 1 ( ET 1 ) , the effect of a recombinant NEP ( rNEP ) on BET 1 and on ET 1 was assessed in vitro . 2 . ^^^ Metabolism of endothelin 1 and big endothelin 1 by recombinant neutral endopeptidase EC . 3 . 4 . 24 . 11 . 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effect of phosphoramidon on the increase in pulmonary inflation pressure ( PIP ) induced by endothelin 1 ( ET 1 ) administered by aerosol in ovalbumin ( OA ) sensitized and challenged guinea pigs was investigated after pretreatment or not of the animals with the neutral endopeptidase inhibitor , phosphoramidon , the cyclooxygenase inhibitor , indomethacin or the platelet activating factor ( PAF ) antagonist , BN 50730 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Neutral endopeptidase ( NEP ) degrades vasoactive peptides , including the natriuretic peptides , angiotensin 2 , and endothelin 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| In a series of experiments , we measured forearm vascular responses to intra arterial norepinephrine ( 30 to 240 pmol / min ) , endothelin 1 ( 5 pmol / min ) , the selective endothelin A ( ETA ) receptor antagonist BQ 123 ( 3 mg / hr ) , the mixed endothelin converting enzyme and neutral endopeptidase inhibitor phosphoramidon ( 30 nmol / min ) , and the selective neutral endopeptidase inhibitor thiorphan ( 30 nmol / min ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| This study was designed to determine whether peroxynitrite induces airway hyperresponsiveness to substance P ( SP ) and endothelin 1 ( ET 1 ) through the inactivation of airway NEP . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) degrades vasoactive peptides , including the natriuretic peptides and endothelin 1 ( ET 1 ) . ^^^ Neutral endopeptidase ( NEP ) degrades vasoactive peptides , including the natriuretic peptides and endothelin 1 ( ET 1 ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The mechanism ( s ) of degradation of the potent vasoconstrictor endothelin 1 ( ET 1 ) by rat vascular smooth muscle A 10 cells , which possess the ETA receptor subtype , was investigated by incubating [ 125I ] ET 1 ( 0 . 1 nM ) with cells for 0 4 h at 37 degrees C in the presence and absence of lysosomal enzyme inhibitors , NH4Cl and chloroquine , and a neutral endopeptidase inhibitor , phosphoramidon . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Rat big endothelin 1 induced bronchoconstriction and vasoconstriction in the isolated perfused rat lung : role of endothelin converting enzyme and neutral endopeptidase 24 . 11 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endothelin 1 ( ET 1 ) is produced from inactive precursor big ET 1 by endothelin converting enzyme 1 ( ECE 1 ) , a membrane bound metalloprotease , structurally similar to another metalloprotease , neutral endopeptidase 24 . 11 ( NEP ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP substrates such as bombesin and endothelin 1 induce cell migration . ^^^ Constitutively expressed NEP , recombinant NEP , and induced NEP expression using a tetracycline repressive expression system inhibited bombesin and endothelin 1 stimulated FAK phosphorylation and cell migration . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| This results from NEP inactivation of its neuropeptide substrates ( bombesin and endothelin 1 ) , which in the absence of NEP stimulate cSrc kinase activity and induce rapid degradation of PKCdelta protein . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Intravenous morphine reduces plasma endothelin 1 concentration through activation of neutral endopeptidase 24 . 11 in patients with myocardial infarction . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Effect of neutral endopeptidase inhibition on the actions of adrenomedullin and endothelin 1 in resistance arteries from patients with chronic heart failure . ^^^ This suggests that neutral endopeptidase inhibition , as a therapeutic strategy , will enhance neither the potentially desirable vascular actions of adrenomedullin nor the potentially unfavorable vascular effects of endothelin 1 in human cardiovascular disease states . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP inhibition increased circulating endothelin 1 ( from 2 . 01 + / 0 . 1 to 2 . 90 + / 0 . 2 pmol / l ; P < 0 . 01 ) , atrial natriuretic peptide ( ANP ; from 21 . 5 + / 2 . 7 to 29 . 6 + / 3 . 7 pmol / l ; P < 0 . 01 ) , and the ANP second messenger cGMP . ^^^ Thus , despite significantly increasing endothelin 1 , NEP inhibition did not adversely influence systemic or renal hemodynamics in transplant patients . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effects on ECE 1 and NEP were assessed by determining the inhibition of big endothelin 1 ( big ET 1 ) induced increases in mean arterial pressure ( MAP ) and increases in plasma atrial natriuretic peptide ( ANP ) concentrations respectively , in conscious rats . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Vasopeptidase inhibitors ( VPI ) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides , bradykinin , and perhaps endothelin 1 in patients with congestive heart failure . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| These data suggest that endothelin 1 contributes to the pathogenesis of chagasic cardiomyopathy and interventions that inhibit the synthesis of endothelin 1 and / or neutral endopeptidase might have a protective effect on myocardial structure and function in murine Chagas ' disease . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Enhanced endothelin 1 degradation by intravenous morphine in patients with congestive heart failure : role of neutral endopeptidase 24 . 11 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Many vasoactive peptides such as atrial natriuretic peptide ( ANP ) and endothelin 1 ( ET 1 ) are degraded by neutral endopeptidase 24 . 11 ( NEP ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| These studies examined the interactions of neutral endopeptidase ( NEP ) , endothelin 1 ( ET 1 ) , and nitric oxide ( NO ) in deoxycorticosterone acetate ( DOCA ) induced hypertension . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endothelin converting enzyme activity was measured using big endothelin 1 as a substrate and thiorphan as an inhibitor of serum neutral endopeptidase . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon , a dual neutral endopeptidase and endothelin converting enzyme inhibitor , blocked both pressor responses to endothelin 1 ( 1 31 ) and big endothelin 1 but not those afforded by endothelin 1 . ^^^ Thiorphan , a neutral endopeptidase inhibitor , markedly inhibited the response to endothelin 1 ( 1 31 ) but only weakly reduced that of big endothelin 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVES : Neutral endopeptidase 24 . 11 ( NEP ) is known to play important roles in the maintenance of homeostasis or in neoplastic transformation and tumor progression in certain human malignancies through the enzymatic inactivation of bioactive peptides such as endothelin 1 ( ET 1 ) , angiotensin 2 , and bombesin . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP is a cell surface metalloprotease that degrades several vasoactive peptides , including endothelin 1 ( ET 1 ) and atrial natriuretic peptide ( ANP ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase degrades atrial natriuretic peptide ( ANP ) and bradykinin and may generate endothelin 1 from big endothelin . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The contribution of the metalloproteases , neutral endopeptidase ( NEP ) and angiotensin converting enzyme ( ACE ) , in the presence or absence of the epithelium lining , by use of specific inhibitors , was also evaluated on the effects of big ET 1 . 2 . ^^^ Incubation of human isolated bronchi with the NEP inhibitor phosphoramidon ( 10 ( 5 ) M ) induced a rightward shift of the concentration response curve induced by big ET 1 ( 10 ( 9 ) M to 3 10 10 ( 7 ) M ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| From these findings , it seems reasonable to consider that phosphoramidon sensitive and membrane bound metalloproteinase , which is not a neutral endopeptidase 24 . 11 , is the most plausible candidate for big ET 1 converting enzyme in vivo . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Intravenous injections of big endothelin ( ET ) 1 ( 700 pmol / kg ) in the pig increased arterial plasma levels of ET 1 like immunoreactivity ( ET 1 LI ) from 11 . 1 + / 0 . 7 pM to 46 . 3 + / 6 . 7 pM in the control situation and from 11 . 5 + / 0 . 4 pM to 58 . 2 + / 17 pM in the presence of the neutral endopeptidase inhibitor phosphoramidon ( 3 mg / kg ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| We have shown that the effects of NEP are mediated by its ability to catalytically inactivate substrates such as bombesin and endothelin 1 , but also through direct protein protein interaction with other protein such as Lyn kinase [ which associates with the p 85 subunit of phosphatidylinositol 3 kinase ( PI 3 K ) resulting in NEP Lyn PI 3 K protein complex ] , ezrin / radixin / moesin ( ERM ) proteins , and the PTEN tumor suppressor protein . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The enzyme neutral endopeptidase ( NEP ) degrades ANP and bradykinin and generates endothelin 1 from big endothelin . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Effects of epithelium removal were partially mimicked by phosphoramidon ( 10 microM ) , an enkephalinase inhibitor , suggesting that enkephalinase ( EC . 3 . 4 . 24 . 11 . ) is able to degrade ET 1 and ET 2 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The sarafotoxins ( SRTXs ) were more resistant than the ETs to NEP : for example , the half time for ET 1 was approximately 1 hr , while it was approximately 4 hr for SRTX b and even higher for SRTX c . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The principal activity in this membrane fraction hydrolyzing ET 1 was identified as endopeptidase 24 . 11 ( EC 3 . 4 . 24 . 11 ) by inhibitory and immunological criteria . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effects of the selective neutral endopeptidase ( EC 3 . 4 . 24 . 11 , NEP ) inhibitor SQ 28 , 603 on endogenous plasma endothelin ( ET ) concentration and on the clearance from the circulation of exogenously administered synthetic human ET 1 were examined in Sprague Dawley rats . ^^^ Inhibition of NEP by SQ 28 , 603 ( 100 mumol / kg intravenously , i . v . ) affected neither basal levels of plasma ET nor the circulatory clearance of an i . v . administered bolus dose ( 3 nmol / kg ) of ET 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| These results indicate that the 108 kDa enzyme probably seems to be a neutral endopeptidase ( EC 3 . 4 . 24 . 11 . ) or similar one , but the 162 kDa enzyme is a unique metalloprotease that converts big ET 1 to ET 1 . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon and SCH 39370 , both inhibitors of neutral endopeptidase 24 . 11 ( NEP ) , markedly inhibited degradation of 125I ET 1 in lung extract and clearly less in kidney extract . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| We have investigated the possible presence of endothelin metabolizing neutral endopeptidase ( NEP , EC 3 . 4 . 24 . 11 ) on A 10 cell membranes using [ 125I ] ET 1 binding and direct measurements of NEP . ^^^ Specific [ 125I ] ET 1 ( 50 pM ) binding ( defined with 100 nM ET 1 ) to A 10 cell membranes was increased in a concentration dependent manner by the selective NEP inhibitors thiorphan , phosphoramidon , and SQ 28 , 603 [ ( + / ) N [ 2 ( mercaptomethyl ) 1 oxo 3 phenylpropyl ] beta alanine ] with EC 50 values of 9 . 4 , 28 . 4 , and 5 . 7 nM respectively . ^^^ ET 1 inhibited A 10 cell NEP , and KNEP with IC 50 values of 30 and 21 . 3 microM respectively . ^^^ These data suggest A 10 cell membranes contain a NEP which has similar characteristics to NEP 24 . 11 , and which actively metabolizes [ 125I ] ET 1 . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| These results suggest that endothelin degradation enzyme on SMC is related to enkephalinase and that this enzyme plays a significant role in the degradation of ET 1 in vivo . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| These results suggest that ET degradation activity in the membrane fractions of the kidney is related to enkephalinase and may be involved in the degradation of ET 1 in vivo . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effect of kelatorphan ( 10 ( 4 ) mol / L ) , a specific inhibitor of neutral endopeptidase 24 . 11 , on the ET 1 induced pressor effect was the same as that seen with phosphoramidon . ^^^ Therefore , the phosphoramidon sensitive ET 1 converting enzyme in the kidney seems to contribute to the functional local conversion of big ET 1 to ET 1 , and neutral endopeptidase 24 . 11 may be responsible for the proteolytic degradation of ET 1 in the kidney . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of big ET 1 induced pressor response by an orally active dual inhibitor of endothelin converting enzyme and neutral endopeptidase 24 . 11 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon and the neutral endopeptidase ( NEP ) inhibitors thiorphan and candoxatrilat blocked the vasoconstriction caused by big ET 1 in endothelium denuded RSA . ^^^ In conclusion , we can speculate that the big ET 1 contraction in RSA is mediated by an ECE , probably present on smooth muscle cells , which is susceptible to NEP inhibitors and is different from the ECE on endothelial cells . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Incubation of strips of GPLP with the dual endothelin converting enzyme ( ECE ) and neutral endopeptidase ( NEP ) inhibitor , phosphoramidon ( 10 microM ) , as well as two other NEP inhibitors thiorphan ( 10 microM ) or SQ 28 , 603 ( 10 microM ) decreased by 43 % ( P < 0 . 05 ) , 42 % ( P < 0 . 05 ) and 40 % ( P < 0 . 05 ) the contractions induced by 30 nM of big ET 1 respectively . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| By using a specific neutral endopeptidase 24 . 11 ( NEP 24 . 11 ) inhibitor , thiorphan , it was also shown that the phosphoramidon sensitive ET 1 degrading activity in this cell line is due to the NEP 24 . 11 activity . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon , a neutral endopeptidase inhibitor , was not able to reveal any biological ( O2 . ) or biochemical ( [ Ca ( 2+ ) ] 1 response to ET 1 in the absence or in the presence of fMLP in these cells . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon , which inhibits neutral endopeptidase , an enzyme reported to degrade ET 1 and also to inhibit the endothelin converting enzyme , potentiated the Sephadex induced rise in ET 1 LI . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| In addition , neutral endopeptidase 24 . 11 ( also called enkephalinase ) , which degrades ET 1 , is expressed in the stromal cells of the endometrium , and the levels of this enzyme ( mRNA , protein and specific activity ) are increased in response to progesterone / progestin . ^^^ Moreover , the expression of ET 1 , PTH rP and enkephalinase is modulated by transforming growth factor beta . ^^^ We hypothesize that the inappropriate expression of ET 1 , enkephalinase and PTH rP in endometrial stromal cells during synthetic progestin administration may be one cause of abnormal endometrial development and erratic endometrial bleeding . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| However phosphoramidon ( 100 microM ) , an inhibitor of ECE and NEP , almost abolished specific binding , indicating that both NEP and ECE cleave big ET 1 in the kidney . ^^^ We conclude that big ET 1 is processed by NEP and ECE in human kidney and that the cleaved product binds predominantly to the ET ( B ) receptor subtype . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Here , the stimulated ( lipopolysaccharide or interleukin 1 beta ) production of ET 1 from guinea pig tracheal epithelial cells was abolished by CGS 26303 or CGS 26393 , two ECE / neutral endopeptidase ( NEP ) inhibitors , but was unaffected by CGS 24592 , a specific NEP inhibitor . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Similarly , 10 ( 3 ) M thiorphan ( a selective inhibitor of the neutral endopeptidase ) did not affect big ET 1 induced contraction , both alone and in combination with phosphoramidon ( 10 ( 3 ) M ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| We conclude that BEAS 2B and A 549 cells are able to process either endogenous or exogenous Big ET 1 by ECE 1 and that isoforms 1b and 1c could be involved in this processing with no significant role of NEP . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| In both groups , ET 1 immunoreactivity in endometrial epithelium was markedly reduced compared with the normal menstrual cycle and did not vary cyclically , while NEP immunoreactivity , particularly in the epithelium , was increased . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| This cytokine stimulated release of ET 1 was inhibited by a series of dual endothelin converting enzyme ( ECE ) / neutral endopeptidase inhibitors , phosphoramidon , CGS 26303 , and CGS 26393 , with an accompanying increase in big ET 1 release but with no effect on expression of mRNA for prepro ET 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Conversely , thiorphan , a selective NEP inhibitor , did not attenuate but rather increased the concentration of ET 1 in cell supernatants . ^^^ CGS 24 592 and SQ 28 603 , other NEP inhibitors , also increased the concentrations of ET 1 in cell supernatants in a concentration dependent manner . ^^^ These data suggest that ET 1 is simultaneously produced and degraded by guinea pig tracheal epithelial cells via phosphoramidon sensitive ECE and NEP pathways , respectively . ^^^ This observation is of interest when considering that asthmatic patients were shown to have a damaged airway epithelium combined with the loss of NEP activity , which was associated with an increased expression and production of ET 1 . . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Responses to ET 1 were unaffected by either the neutral endopeptidase ( NEP ) inhibitor thiorphan ( 10 ( 5 ) M ) or by the dual NEP / ECE inhibitor phosphoramidon ( 10 ( 5 ) M ) . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Increases in [ Ca2+ ] 1 caused by ET 1 ( 1 31 ) , big ET 1 and ET 2 ( 1 31 ) were completely inhibited by 10 ( 4 ) M phosphoramidon , a dual neutral endopeptidase ( NEP ) / endothelin converting enzyme ( ECE ) inhibitor , and 10 ( 5 ) M thiorphan , a NEP inhibitor . ^^^ These results suggest that ET 1 ( 1 31 ) , big ET 1 and ET 2 ( 1 31 ) cause an increase in [ Ca2+ ] 1 by being converted into the corresponding ET 1 and ET 2 by NEP , but this did not occur with big ET 2 in human BSMC . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| It now appears to be evident , especially from human experiments on forearm blood flow after intra arterial infusion of agents , that NEP inhibitor induced vasoconstriction is mediated by increased ET 1 rather than by angiotensin 2 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Despite apparent structural similarities , ECE 1 cleaves big ET 1 exclusively between Trp ( 21 ) and Val ( 22 ) , in contrast to neprilysin , which cleaves big ET 1 at various sites . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The enzyme with a pH optimum 4 . 5 is of lysosomal origin whereas the two other enzymes correspond by their pH optima to the renal ET 1 peptidase and neutral endopeptidase . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| We sought to demonstrate the distribution of the 2 ECE 1 isoforms in experimental atherosclerosis , to determine the effects of chronic NEP 1 on plasma cGMP concentrations , vascular wall ECE 1 activity , and ET 1 concentration , and to correlate these actions with atheroma formation . ^^^ Our hypothesis was that chronic NEP 1 , in association with augmented cGMP , would inhibit ECE 1 conversion of big ET 1 to active ET 1 , thus reducing tissue ET 1 concentrations and associated atheroma formation . ^^^ Compared with control values , plasma cGMP concentrations were increased ( 2 . 8+ / 0 . 6 versus 8 . 4+ / 1 . 2 pmol / mL , P < 0 . 05 ) , ECE 1 activity was attenuated ( 68+ / 3 % versus 32+ / 8 % , P < 0 . 05 ) , aortic tissue ET 1 concentrations were reduced ( 4 . 6+ / 0 . 5 versus 3 . 2+ / 0 . 3 pg / mg protein , P < 0 . 05 ) , and atheroma formation was attenuated ( 62+ / 6 % versus 34+ / 5 % , P < 0 . 01 ) by NEP 1 . ^^^ |
|
| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Therefore , compounds that can suppress the production of ET 1 by inhibiting ECE while simultaneously potentiating the levels of ANP by inhibiting NEP may be novel agents for the treatment of cardiovascular and renal dysfunction . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| METHODS : Levels of VEGF and ET 1 were measured by enzyme linked immunosorbent assay and expression of neutral endopeptidase ( NEP , CD 10 ) , known to degrade ET 1 , was quantified by flow cytometric analysis after cell trypsinization . ^^^ Addition of a neutralizing anti CD 10 antibody to fibroblast cultures downregulated CD 10 expression at the cell surface without changing ET 1 levels in cell supernatants after 24 or 48 h . ^^^ This suggests that membrane bound NEP has minimal or no activity against secreted ET 1 . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Conversely , thiorphan , a specific inhibitor of neutral endopeptidase ( NEP ) , rather increased the levels of ET 1 secretion mainly after UVB irradiation . ^^^ Taken together , the results showed that normal human keratinocytes secrete and partly degrade ET 1 through ECE and NEP pathways and pointed out a differential regulation of ET 1 by UVB and UVA 1 radiations without any noticeable role for PGE2 . . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| However , inhibitors of neutral endopeptidase ( thiorphan ) and matrix metalloproteases ( batimistat ) did not affect the conversion of big ET 1 to ET 1 . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Peptide bioavailability and potency can be regulated through hypoxic up and down regulation of synthesis or release , activation by converting enzymes ( ACE for AII and ECE for ET 1 ) , inactivation by neutral endopeptidase and proteases , or by interaction with nitric oxide ( NO ) . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| However , there was a highly significant augmentation in the NEP inhibited segments , consistent with an inhibition of ET 1 degradation ( median difference , 16 . 8 ; 95 % CI , 23 . 5 , 10 . 4 ; P = . 002 , Wilcoxon ) . ^^^ ECE immunostaining was reduced in the ECE / NEP inhibited veins , although ET 1 staining was also present . ^^^ ET 1 expression was intense in the thickened neointimas of NEP inhibited veins , which also showed significant ECE staining . ^^^ Elevated levels of big ET 1 were measured in the ECE / NEP inhibited veins , consistent with reduced ECE activity . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Thiorphan ( 0 . 25 and 2 . 5 mg kg ( 1 ) ) did not affect the pressor responses to ET 1 ( 1 31 ) although its PIP effects were markedly reduced by the NEP inhibitor . ^^^ We suggest that , in order to raise MAP , ET 1 ( 1 31 ) requires conversion to ET 1 , predominantly by ECE and to a lesser extent neutral endopeptidase 24 . 11 , whereas the reverse holds true regarding its pharmacological effects in airways . . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Finally , using the neutral endopeptidase 24 . 11 ( NEP 24 . 11 ) inhibitor , thiorphan , we determined the involvement of this enzyme on ET 1 ( 1 31 ) effects . ^^^ We therefore suggest that NEP 24 . 11 in the pulmonary vasculature , is implicated in the cleavage of ET 1 ( 1 31 ) to produce ET 1 which will further act on both ET receptors . . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The present study examined the roles of endothelin converting enzyme ( ECE ) , neutral endopeptidase ( NEP ) and mast cell chymase as processors of the endothelin ( ET ) analogues ET 1 ( 1 21 ) , ET 1 ( 1 31 ) and big ET 1 in the trachea of allergic mice . ^^^ The NEP inhibitor CGS 24592 ( 10 microM ) inhibited contractions induced by ET 1 ( 1 31 ) ( 6 . 2 fold rightward shift ; P < 0 . 05 ) but not ET 1 ( 1 21 ) or big ET 1 . ^^^ If endogenous ET 1 ( 1 31 ) is formed within allergic airways , it is likely to undergo further conversion by NEP to more active products . . ^^^ Role of endothelin converting enzyme , chymase and neutral endopeptidase in the processing of big ET 1 , ET 1 ( 1 21 ) and ET 1 ( 1 31 ) in the trachea of allergic mice . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Additionally , by measuring the production of ET 1 ( 1 31 ) , we showed that a chymase like enzyme is involved in this process when ECE and NEP are inhibited by phosphoramidon . ^^^ Finally , we showed that NEP is the predominant enzymatic pathway involved in the cleavage of ET 1 ( 1 31 ) to a bioactive metabolite that will act on ET ( A ) receptors to induce contraction in the rabbit aorta . . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| While ACE and ECE are respectively involved in the transformation of angiotensin 1 and Big ET into angiotensin 2 and ET 1 respectively , which possess vasoconstrictor and mitogenic properties , NEP is involved in the degradation of atrial natriuric factor ( ANF ) , which possesses vasorelaxant , diuretic / natriuretic and antihypertrophic properties . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| The mRNA expressions of renin , angiotensin converting enzyme ( ACE ) , type 1 angiotensin 2 receptor ( AT1R ) , ET 1 , type A ET receptor ( ET ( A ) ) , and neutral endopeptidase ( NEP ) were determined in the thoracic aorta by reverse transcription polymerase chain reaction . ^^^ The expression of ET 1 and ET ( A ) mRNA was increased , whereas that of NEP mRNA decreased . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| While neutral endopeptidase ( NEP ) and matrix metalloproteinase 2 ( MMP 2 ) are able to process big ET 1 , inhibitors of NEP ( thiorphan ) and MMP ( batimistat ) did not affect ECE 1 activity . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Other enzymes , such as the neutral endopeptidase 24 11 , is curiously not only involved in the degradation and inactivation of ET 1 , but is also responsible for the final production of the peptide via the hydrolysis of ET 1 ( 1 31 ) . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 ( NEP ) is a cell surface aminopeptidase with a ubiquitous expression and is capable of degrading a number of bioactive peptides including ET 1 . ^^^ We showed that there was a significant decrease in cell proliferation and invasiveness with a reduction in the concentration of ET 1 in the conditioned medium on the NEP overexpression of NEP in ovarian carcinoma cells . ^^^ This evidence suggests that NEP functionally suppresses the progression of ovarian carcinoma and further study of this enzyme may reveal an effective way to target ET 1 for the treatment of this carcinoma . . ^^^ Neutral endopeptidase 24 . 11 ( NEP ) is a cell surface aminopeptidase with a ubiquitous expression and is capable of degrading a number of bioactive peptides including ET 1 . ^^^ |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P05305 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
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