The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom

The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom

Autor Lameu, Claudiana Google Scholar
Hayashi, Mirian Akemi Furuie Autor UNIFESP Google Scholar
Guerreiro, Juliano R. Google Scholar
Oliveira, Eduardo F. Google Scholar
Lebrun, Ivo Google Scholar
Pontieri, Vera Google Scholar
Morais, Katia L. P. Google Scholar
Camargo, Antonio C. M. Google Scholar
Ulrich, Henning Google Scholar
Instituição Universidade de São Paulo (USP)
Inst Butantan
Universidade Federal de São Paulo (UNIFESP)
Resumo Pyroglutamyl proline-rich oligopeptides, present in the venom of the pit viper Bothrops jararaca (Bj-PROs), are the first described naturally occurring inhibitors of the angiotensin I-converting enzyme (ACE). the inhibition of ACE by the decapeptide Bj-PRO-10c (<ENWPHPQIPP) and other Bj-PROs was classically used to explain the pharmacological effects of these venom peptides in mammals resulting in a decrease of blood pressure. Recent studies, however, suggest that ACE inhibition alone is not sufficient for explaining the antihypertensive actions exerted by these peptides. in this study, we show that intracerebroventricular injection of Bj-PRO-10c induced a significant reduction of mean arterial pressure (MAP) together with a decrease of heart rate (HR) in spontaneously hypertensive rats, indicating that Bj-PRO-10c may act on the central nervous system. in agreement with its supposed neuronal action, this peptide dose-dependently evoked elevations of intracellular calcium concentration ([Ca(2+)](i)) in primary culture from postnatal rat brain. the N-terminal sequence of the peptide was not essential for induction of calcium fluxes, while any changes of C-terminal Pro or Ile residues affected Bj-PRO-10c's activity. Using calcium imaging by confocal microscopy and fluorescence imaging plate reader analysis, we have characterized Bj-PRO-10c-induced [Ca(2+)](i) transients in rat brain cells as being independent from bradykinin-mediated effects and ACE inhibition. Bj-PRO-10c induced pertussis toxin-sensitive G(i/o)-protein activity mediated through a yet unknown receptor, influx and liberation of calcium from intracellular stores, as well as reduction of intracellular cAMP levels. Bj-PRO-10c promoted glutamate and GABA release that may be responsible for its antihypertensive activity and its effect on HR. (C) 2010 International Society for Advancement of Cytometry
Assunto pyroglutamyl proline-rich oligopeptides
calcium signaling
G-protein coupled receptor
neurotransmitter release
cardiovascular homeostasis
neuronal cells
snake peptide
calcium imaging by confocal microscopy
fluorescence imaging plate reader analysis
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Data 2010-03-01
Publicado em Cytometry Part A. Hoboken: Wiley-liss, v. 77A, n. 3, p. 220-230, 2010.
ISSN 1552-4922 (Sherpa/Romeo, fator de impacto)
Editor Wiley-Blackwell
Extensão 220-230
Fonte http://dx.doi.org/10.1002/cyto.a.20860
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000276107800005
URI http://repositorio.unifesp.br/handle/11600/32278

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