{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:32:37Z","timestamp":1783971157646,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,9,2]],"date-time":"2010-09-02T00:00:00Z","timestamp":1283385600000},"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":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proline\u2010rich peptides from <jats:italic>Bothrops jararaca<\/jats:italic> venom (<jats:italic>Bj<\/jats:italic>\u2010PRO) were characterized based on the capability to inhibit the somatic angiotensin\u2010converting enzyme. The pharmacological action of these peptides resulted in the development of Captopril, one of the best examples of a target\u2010driven drug discovery for treatment of hypertension. However, biochemical and biological properties of <jats:italic>Bj<\/jats:italic>\u2010PROs were not completely elucidated yet, and many recent studies have suggested that their activity relies on angiotensin\u2010converting enzyme\u2010independent mechanisms. Here, we show that <jats:italic>Bj<\/jats:italic>\u2010PRO\u20107a (&lt;EDGPIPP) specifically activates [Ca<jats:sup>2+<\/jats:sup>]<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> transients in CHO\u2010M1 cells expressing heterologous rat M1 muscarinic subtype. The activation curve established by microfluorimetry in CHO\u2010M1 cells using increasing concentrations of <jats:italic>Bj<\/jats:italic>\u2010PRO\u20107a reached the maximum response in the presence of 3 \u03bc<jats:italic>M<\/jats:italic>\n<jats:italic>Bj<\/jats:italic>\u2010PRO\u20107a (EC<jats:sub>50<\/jats:sub> = 0.25 \u00b1 0.07 \u03bc<jats:italic>M<\/jats:italic>). The variation observed by calcium imaging in these cells ranged from 52 to 1218 n<jats:italic>M<\/jats:italic> (EC<jats:sub>50<\/jats:sub> = 0.31 \u00b1 0.12 \u03bc<jats:italic>M<\/jats:italic>). [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>\n<jats:italic>i<\/jats:italic><\/jats:sub> responses in CHO\u2010M1 cells were largely inhibited by pirenzepine, a specific M1 antagonist. Neural\u2010differentiated P19 cells expressing endogenous M1 receptors were also responsive to <jats:italic>Bj<\/jats:italic>\u2010PRO\u20107a application, whereas no such response was observed in undifferentiated P19 cells not expressing muscarinic receptors. As further support for its specific action on M1 receptors, the peptide did not activate M3 subtypes in transfected CHO cells. Our findings provide a novel M1 muscarinic receptor agonist that could be used for basic research and even for pharmacological applications. \u00a9 2010 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.20963","type":"journal-article","created":{"date-parts":[[2010,9,3]],"date-time":"2010-09-03T17:37:10Z","timestamp":1283535430000},"page":"77-83","source":"Crossref","is-referenced-by-count":27,"title":["The snake venom peptide <i>Bj<\/i>\u2010PRO\u20107a is a M1 muscarinic acetylcholine receptor agonist"],"prefix":"10.1002","volume":"79A","author":[{"given":"Priscilla D.","family":"Negraes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudiana","family":"Lameu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirian A. 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