{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:48:50Z","timestamp":1784033330382,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3591,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Pilocarpine, a muscarinic acetylcholine receptor (mAChR) agonist, is widely used for treatment of xerostomia and glaucoma. It can also cause many other cellular responses by activating different subtypes of mAChRs in different tissues. However, the potential role of pilocarpine in modulating cardiac function remained unstudied.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We found that pilocarpine produced concentration\u2010dependent (0.1\u201310\u2003\u03bc<jats:sc>M<\/jats:sc>) decrease in sinus rhythm and action potential duration, and hyperpolarization of membrane potential in guinea\u2010pig hearts. The effects were nearly completely reversed by 1\u2003\u03bc<jats:sc>M<\/jats:sc> atropine or 2\u2003n<jats:sc>M<\/jats:sc> 4DAMP methiodide (an M<jats:sub>3<\/jats:sub>\u2010selective antagonist).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Patch\u2010clamp recordings in dispersed myocytes from guinea\u2010pig and canine atria revealed that pilocarpine induces a novel K<jats:sup>+<\/jats:sup> current with delayed rectifying properties. The current was suppressed by low concentrations of M<jats:sub>3<\/jats:sub>\u2010selective antagonists 4DAMP methiodide (2\u201310\u2003n<jats:sc>M<\/jats:sc>), 4DAMP mustard (4\u201320\u2003n<jats:sc>M<\/jats:sc>, an ackylating agent) and <jats:italic>p<\/jats:italic>\u2010F\u2010HHSiD (20\u2013200\u2003n<jats:sc>M<\/jats:sc>). Antagonists towards other subtypes (M<jats:sub>1<\/jats:sub>, M<jats:sub>2<\/jats:sub> or M<jats:sub>4<\/jats:sub>) all failed to alter the current.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The affinity of pilocarpine (<jats:italic>K<jats:sub>D<\/jats:sub><\/jats:italic>) at mAChRs derived from displacement binding of [<jats:sup>3<\/jats:sup>H]\u2010NMS in the homogenates from dog atria was 2.2\u2003\u03bc<jats:sc>M<\/jats:sc> (65% of the total binding) and that of 4DAMP methiodide was 2.8\u2003n<jats:sc>M<\/jats:sc> (70% of total binding), consistent with the concentration of pilocarpine needed for the current induction and for the modulation of the cardiac electrical activity and the concentration of 4DAMP to block pilocarpine effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data indicate, for the first time, that pilocarpine modulates the cellular electrical properties of the hearts, likely by activating a K<jats:sup>+<\/jats:sup> current mediated by M<jats:sub>3<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 1725\u20131734; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702486\">10.1038\/sj.bjp.0702486<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702486","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:58:52Z","timestamp":1106942332000},"page":"1725-1734","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Pilocarpine modulates the cellular electrical properties of mammalian hearts by activating a cardiac M<sub>3<\/sub> receptor and a K<sup>+<\/sup> current"],"prefix":"10.1111","volume":"126","author":[{"given":"Huizhen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890090303"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1986.tb11189.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0020-711X(94)90178-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-8673.1990.tb00023.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00124-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.1.C42"},{"key":"e_1_2_7_8_1","first-page":"1133","article-title":"Inhibition of outflow facility and accommodative and miotic responses to pilocarpine in rhesus monkeys by muscarinic receptor subtype antagonists","volume":"263","author":"GABELT B.T.","year":"1992","journal-title":"J. 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