{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:11:53Z","timestamp":1790007113767,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":242,"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":[[2008,6]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>In the ciliary muscle, the tonic component of the contraction produced by cholinergic agonists is highly dependent on Ca<jats:sup>2+<\/jats:sup> provided by influx through non\u2010selective cation channels (NSCCs) opened by stimulation of M<jats:sub>3<\/jats:sub> muscarinic receptors. We examined effects of YM\u2010254890 (YM), a G<jats:sub>q\/11<\/jats:sub>\u2010specific inhibitor, on contraction, NSCC currents and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> elevation induced by carbachol (CCh).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Isometric tension was recorded from ciliary muscle bundles excised from bovine eyes. In ciliary myocytes dispersed with collagenase and cultured for 1\u20135 days, whole\u2010cell currents were recorded by voltage clamp and the intracellular free Ca<jats:sup>2+<\/jats:sup> concentration [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was monitored using the Fluo\u20104 fluorophore. Existence and localization of M<jats:sub>3<\/jats:sub> receptors and the \u03b1 subunit of G<jats:sub>q\/11<\/jats:sub> (G\u03b1<jats:sub>q\/11<\/jats:sub>) were examined by immunofluorescence microscopy using AlexaFluor\u2010conjugated antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Both phasic and tonic components of contractions evoked by 2\u2003\u03bcM CCh were inhibited by YM (3\u201310\u2003\u03bcM) in a dose\u2010dependent manner. In the cultured cells, CCh (0.05\u201310\u2003\u03bcM) evoked an NSCC current as well as an elevation of the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Both initial and sustained phases of these CCh\u2010evoked responses were abolished by YM (3\u201310\u2003\u03bcM). Immunostaining of the cytoplasmic side of the plasma membrane of ciliary myocytes revealed a dense distribution of M<jats:sub>3<\/jats:sub> receptors and G\u03b1<jats:sub>q\/11<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>The tonic as well as phasic component of the ciliary muscle contraction appears to be under control of signals conveyed by a G<jats:sub>q\/11<\/jats:sub>\u2010coupled pathway. YM is a useful tool to assess whether G<jats:sub>q\/11<\/jats:sub> is involved in a signal transduction system.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>154<\/jats:bold>, 890\u2013900; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.140\">10.1038\/bjp.2008.140<\/jats:ext-link>; published online 21 April 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/bjp.2008.140","type":"journal-article","created":{"date-parts":[[2008,6,9]],"date-time":"2008-06-09T10:18:52Z","timestamp":1213006732000},"page":"890-900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Examination of signalling pathways involved in muscarinic responses in bovine ciliary muscle using YM\u2010254890, an inhibitor of the G<sub>q\/11<\/sub> protein"],"prefix":"10.1111","volume":"154","author":[{"given":"F","family":"Yasui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Miyazu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Naruse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.096875"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707199"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1982.tb09353.x"},{"key":"e_1_2_8_5_1","first-page":"193","article-title":"Muscarinic subsensitivity without receptor change in monkey ciliary muscle","volume":"84","author":"Barany EH","year":"1985","journal-title":"Br J Pharmacol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb09403.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-2873-3"},{"key":"e_1_2_8_8_1","first-page":"2431","article-title":"Ciliary muscle muscarinic binding sites, choline acetyltransferase, and acetylcholinesterase in aging rhesus monkeys","volume":"31","author":"Gabelt BT","year":"1990","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.61.6.727"},{"key":"e_1_2_8_10_1","first-page":"197","volume-title":"Adler's Physiology of the Eye: Clinical Application","author":"Glasser A","year":"2003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000267472"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.118372"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1986.tb10244.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(97)00312-1"},{"key":"e_1_2_8_15_1","first-page":"3732","article-title":"Muscarinic effects on cellular functions in cultured human ciliary muscle cells","volume":"35","author":"Matsumoto S","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.1994.10.125"},{"key":"e_1_2_8_17_1","first-page":"1876","article-title":"Single\u2010cell contraction assay for human ciliary muscle cells. 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