Navegando por Palavras-chave "kininases"

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    Neutral endopeptidase expression in mesangial cells
    (J R A A S Ltd, 2003-12-01) Ebihara, Fabiana [UNIFESP]; Di Marco, Giovana Seno [UNIFESP]; Juliano, Maria Aparecida [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    In the kidney, neutral endopeptidase (NEP) is implicated in the metabolism of several peptides involved in blood pressure and sodium homeostasis control, such as the atrial natriuretic peptide, bradykinin and angiotensin I. Due to its physiological importance in the modulation of pressor responses, the presence of NEP in mouse mesangial cells has been investigated, since these cells control glomerular function and are able to synthesise components of the renin-angiotensin system. A NEP-like activity (NEP-like) that cleaves the fluorogenic substrates Abz-BKQ-EDDnp and AbZ-DRRL-EDDnp was purified from mesangial cell lysate by ion-exchange, followed by gel filtration chromatography. The enzyme was able to hydrolyse bradykinin at the G(4)-F-5 peptide bond and was inhibited by thiorphan. A pH study established that enzyme activity was maximal at pH 7.5 and the determined K-m was 4.86 muM using AbZ-DRRL-EDDnp as substrate. NEP-like was recognised by monoclonal anti-NEP and had a molecular mass of 95 kDa. The purified enzyme was sequenced and showed similarity with human, rat, mouse and rabbit NEPs. We isolated, for the first time, NEP-like from mesangial cells. This enzyme could have an important role in the renal physiology by its action upon different peptides that are able to alter renal haemodynamics.
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    Thimet oligopeptidase EC 3.4.24.15 is a major liver kininase
    (Elsevier B.V., 2000-06-23) Molina, H. M.; Carmona, A. K.; Kouyoumdjian, M.; Borges, D. R.; Universidade Federal de São Paulo (UNIFESP)
    Bradykinin (BK) is a potent hepato-portal hypertensive agent although it is efficiently inactivated by the liver. the organ converts angiotensin I to All, but at a much slower rate than it inactivates BK, We had previously identified EC 3.4.24.15 as an hepatic bradykinin inactivating endopeptidase that hydrolyzes BE; at the F-5-S-6 bond. the aim of this study was to determine the relative importance of BIE, as compared to other kininases, in normal, cirrhotic or inflamed rat livers, as well as in samples of human liver. Using specific substrates and inhibitors we showed that: 1) purified BIE preparation hydrolyzed BE( and a BK analogue (BK-Q) with similar efficacy; BK-Q was functionally active since it caused an increase in hepato-portal pressure, as did BK itself. 2) BK degradation in rat serum was performed by ACE since BIE and prolylendopeptidase (PEP) activities were negligible. 3) normal rat liver homogenate contained a large amount of BIE activity which was eliminated by a specific EC 3.4.24.15 inhibitor; ACE and PEP activities were negligible. 4) Then was no difference (p>0.05) in BIE activity in the liver homogenates from rats with normal, inflamed or cirrhotic livers. 5) BIE activity was efficiently removed from livers (normal, inflamed or cirrhotic) that were perfused with TritonX-100. 6) Human liver had an similar enzymatic pattern although ACE activity was detected. We concluded that in normal, inflamed or cirrhotic rat livers, as well as in the human liver, the bradykinin inactivating endopeptidase CEC 3.3.24.15), and not ACE, is the major hepatic kininase. (C) 2000 Elsevier Science inc. All rights reserved.