{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:14:11Z","timestamp":1791357251770,"version":"4.3.1"},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2830,"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":[[2001,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Muscarinic m1 receptors are inhibited by local anaesthetics (LA) at n<jats:sc>M<\/jats:sc> concentrations. To elucidate in more detail the site(s) of LA interaction, we compared these findings with LA effects on m3 muscarinic receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We expressed receptors in <jats:italic>Xenopus<\/jats:italic> oocytes. Using two\u2010electrode voltage clamp, we measured the effects of lidocaine, QX314 (permanently charged) and benzocaine (permanently uncharged) on Ca<jats:sup>2+<\/jats:sup>\u2010activated Cl<jats:sup>\u2212<\/jats:sup>\u2010currents (<jats:italic>I<\/jats:italic><jats:sub>Cl(Ca)<\/jats:sub>), elicited by acetyl\u2010\u03b2\u2010methylcholine bromide (MCh). We also characterized the interaction of lidocaine with [<jats:sup>3<\/jats:sup>H]\u2010quinuclydinyl benzylate ([<jats:sup>3<\/jats:sup>H]\u2010QNB) binding to m3 receptors. Antisense\u2010injection was used to determine the role of specific G\u2010protein \u03b1 subunits in mediating the inhibitory effects of LA. Using chimeric receptor constructs we investigated which domains of the muscarinic receptors contribute to the binding site for LA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Lidocaine inhibited m3\u2010signalling in a concentration\u2010dependent, reversible, non\u2010competitive manner with an IC<jats:sub>50<\/jats:sub> of 370\u2003n<jats:sc>M<\/jats:sc>, approximately 21 fold higher than the IC<jats:sub>50<\/jats:sub> (18\u2003n<jats:sc>M<\/jats:sc>) reported for m1 receptors. Intracellular inhibition of both signalling pathways by LA was similar, and dependent on the G<jats:sub>q<\/jats:sub>\u2010 protein \u03b1 subunit. In contrast to results reported for the m1 receptor, the m3 receptor lacks the major extracellular binding site for charged LA. The N\u2010terminus and third extracellular loop of the m1 muscarinic receptor molecule were identified as requirements to obtain extracellular inhibition by charged LA.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>133<\/jats:bold>, 207\u2013216; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704040\">10.1038\/sj.bjp.0704040<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704040","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:24:05Z","timestamp":1106947445000},"page":"207-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Inhibition of m3 muscarinic acetylcholine receptors by local anaesthetics"],"prefix":"10.1111","volume":"133","author":[{"given":"Markus W","family":"Hollmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten H","family":"Ritter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Henle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"De Klaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesan L","family":"Kamatchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel E","family":"Durieux","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":"10.1097\/00004311-198902740-00005"},{"key":"e_1_2_7_3_1","first-page":"A52","article-title":"Cholinergic mechanisms mediating propofol\u2010induced loss of consciousness in man","volume":"45","author":"BONHOMME V.","year":"1998","journal-title":"Can. 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