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

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dc.contributor.authorLameu, Claudiana
dc.contributor.authorHayashi, Mirian Akemi Furuie [UNIFESP]
dc.contributor.authorGuerreiro, Juliano R.
dc.contributor.authorOliveira, Eduardo F.
dc.contributor.authorLebrun, Ivo
dc.contributor.authorPontieri, Vera
dc.contributor.authorMorais, Katia L. P.
dc.contributor.authorCamargo, Antonio C. M.
dc.contributor.authorUlrich, Henning
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInst Butantan
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:59:20Z
dc.date.available2016-01-24T13:59:20Z
dc.date.issued2010-03-01
dc.description.abstractPyroglutamyl 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 Cytometryen
dc.description.affiliationUniv São Paulo, Inst Quim, Dept Bioquim, BR-05508900 São Paulo, Brazil
dc.description.affiliationInst Butantan, Ctr Appl Toxinol CAT CEPID, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, ESALQ, Dept Ciencias Biol, Lab Bioquim Peptideos & Prot, BR-05508900 São Paulo, Brazil
dc.description.affiliationInst Butantan, Lab Bioquim & Biofis, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Dept Dev & Cell Biol, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifespDepartment of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent220-230
dc.identifierhttp://dx.doi.org/10.1002/cyto.a.20860
dc.identifier.citationCytometry Part A. Hoboken: Wiley-liss, v. 77A, n. 3, p. 220-230, 2010.
dc.identifier.doi10.1002/cyto.a.20860
dc.identifier.issn1552-4922
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32278
dc.identifier.wosWOS:000276107800005
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofCytometry Part A
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectpyroglutamyl proline-rich oligopeptidesen
dc.subjectcalcium signalingen
dc.subjectG-protein coupled receptoren
dc.subjectneurotransmitter releaseen
dc.subjectcardiovascular homeostasisen
dc.subjectneuronal cellsen
dc.subjectsnake peptideen
dc.subjectcalcium imaging by confocal microscopyen
dc.subjectfluorescence imaging plate reader analysisen
dc.titleThe Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venomen
dc.typeinfo:eu-repo/semantics/article
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