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Title: Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes vasodilatation mediated by both bradykinin B-2 and M1 muscarinic acetylcholine receptors
Authors: Morais, Katia Luciano Pereira [UNIFESP]
Hayashi, Mirian Akemi Furuie [UNIFESP]
Bruni, F. M.
Lopes-Ferreira, M.
Camargo, Antonio Carlos Martins de [UNIFESP]
Ulrich, H.
Lameu, C.
Inst Butantan
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Keywords: Bradykinin-potentiating peptides
Bradykinin B-2 receptor
Muscarinic acetylcholine receptor
Nitric oxide
Proline-rich oligopeptide
Issue Date: 15-Mar-2011
Publisher: Elsevier B.V.
Citation: Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 81, n. 6, p. 736-742, 2011.
Abstract: Bradykinin-potentiating peptides (BPPs) or proline-rich oligopeptides (PROs) isolated from the venom glands of Bothrops jararaca (Bj) were the first natural inhibitors of the angiotensin-converting enzyme (ACE) described. Bj-PRO-5a (< EKWAP), a member of this structurally related peptide family, was essential for the development of captopril, the first site-directed ACE inhibitor used for the treatment of human hypertension. Nowadays, more Bj-PROs have been identified with higher ACE inhibition potency compared to Bj-PRO-5a. However, despite its modest inhibitory effect of ACE inhibition, Bj-PRO-5a reveals strong bradykinin-potentiating activity, suggesting the participation of other mechanisms for this peptide. in the present study, we have shown that Bj-PRO-5a induced nitric oxide (NO) production depended on muscarinic acetylcholine receptor M1 subtype (mAchR-M1) and bradykinin B-2 receptor activation, as measured by a chemiluminescence assay using a NO analyzer. Intravital microscopy based on transillumination of mice cremaster muscle also showed that both bradykinin B-2 receptor and mAchR-M1 contributed to the vasodilatation induced by Bj-PRO-5a. Moreover, Bj-PRO-5a-mediated vasodilatation was completely blocked in the presence of a NO synthase inhibitor. the importance of this work lies in the definition of novel targets for Bj-PRO-5a in addition to ACE, the structural model for captopril development. (C) 2011 Elsevier Inc. All rights reserved.
ISSN: 0006-2952
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