{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:18:13Z","timestamp":1778887093867,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,1,22]],"date-time":"2010-01-22T00:00:00Z","timestamp":1264118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pyroglutamyl proline\u2010rich oligopeptides, present in the venom of the pit viper<jats:italic>Bothrops jararaca<\/jats:italic>(<jats:italic>Bj<\/jats:italic>\u2010PROs), are the first described naturally occurring inhibitors of the angiotensin I\u2010converting enzyme (ACE). The inhibition of ACE by the decapeptide<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c (&lt;ENWPHPQIPP) and other<jats:italic>Bj<\/jats:italic>\u2010PROs 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<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c induced a significant reduction of mean arterial pressure (MAP) together with a decrease of heart rate (HR) in spontaneously hypertensive rats, indicating that<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c may act on the central nervous system. In agreement with its supposed neuronal action, this peptide dose\u2010dependently evoked elevations of intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>) in primary culture from postnatal rat brain. The N\u2010terminal sequence of the peptide was not essential for induction of calcium fluxes, while any changes of C\u2010terminal Pro or Ile residues affected<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c's activity. Using calcium imaging by confocal microscopy and fluorescence imaging plate reader analysis, we have characterized<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c\u2010induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>transients in rat brain cells as being independent from bradykinin\u2010mediated effects and ACE inhibition.<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c induced pertussis toxin\u2010sensitive G<jats:sub>i\/o<\/jats:sub>\u2010protein activity mediated through a yet unknown receptor, influx and liberation ofcalcium from intracellular stores, as well as reduction of intracellular cAMP levels.<jats:italic>Bj<\/jats:italic>\u2010PRO\u201010c promoted glutamate and GABA release that may be responsible for its antihypertensive activity and its effect on HR. \u00a9 2010 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.20860","type":"journal-article","created":{"date-parts":[[2010,1,22]],"date-time":"2010-01-22T16:18:43Z","timestamp":1264177123000},"page":"220-230","source":"Crossref","is-referenced-by-count":26,"title":["The central nervous system as target for antihypertensive actions of a proline\u2010rich peptide from<i>Bothrops jararaca<\/i>venom"],"prefix":"10.1002","volume":"77A","author":[{"given":"Claudiana","family":"Lameu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirian A. 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