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CB<jats:sub>1<\/jats:sub>signalling was investigated in a cell line derived from human TM (hTM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>CB<jats:sub>1<\/jats:sub>signalling was investigated using ratiometric Ca<jats:sup>2+<\/jats:sup>imaging, western blotting and infrared In\u2010Cell Western analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>WIN55212\u20102, a synthetic aminoalkylindole cannabinoid receptor agonist (10\u2013100\u2003\u03bc<jats:sc>M<\/jats:sc>) increased intracellular Ca<jats:sup>2+<\/jats:sup>in hTM cells. WIN55,212\u20102\u2010mediated Ca<jats:sup>2+<\/jats:sup>increases were blocked by AM251, a CB<jats:sub>1<\/jats:sub>antagonist, but were unaffected by the CB<jats:sub>2<\/jats:sub>antagonist, AM630. The WIN55,212\u20102\u2010mediated increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>was pertussis toxin (PTX)\u2010insensitive, therefore, independent of G<jats:sub>i\/o<\/jats:sub>coupling, but was attenuated by a dominant negative G\u03b1<jats:sub>q\/11<\/jats:sub>subunit, implicating a G<jats:sub>q\/11<\/jats:sub>signalling pathway. The increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>was dependent upon PLC activation and mobilization of intracellular Ca<jats:sup>2+<\/jats:sup>stores. A PTX\u2010sensitive increase in extracellular signal\u2010regulated kinase (ERK1\/2) phosphorylation was also observed in response to WIN55,212\u20102, indicative of a G<jats:sub>i\/o<\/jats:sub>signalling pathway. CB<jats:sub>1<\/jats:sub>\u2010G<jats:sub>q\/11<\/jats:sub>coupling to activate PLC\u2010dependent increases in Ca<jats:sup>2+<\/jats:sup>appeared to be specific to WIN55,212\u20102 and were not observed with other CB<jats:sub>1<\/jats:sub>agonists, including CP55,940 and methanandamide. CP55940 produced PTX\u2010sensitive increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>at concentrations \u226515\u2003\u03bc<jats:sc>M<\/jats:sc>, and PTX\u2010sensitive increases in ERK1\/2 phosphorylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>This study demonstrates that endogenous CB<jats:sub>1<\/jats:sub>couples to both G<jats:sub>q\/11<\/jats:sub>and G<jats:sub>i\/o<\/jats:sub>in hTM cells in an agonist\u2010dependent manner. Cannabinoid activation of multiple CB<jats:sub>1<\/jats:sub>signalling pathways in TM tissue could lead to differential changes in aqueous humour outflow and IOP.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2007)<jats:bold>152<\/jats:bold>, 1111\u20131120; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707495\">10.1038\/sj.bjp.0707495<\/jats:ext-link>; published online 8 October 2007<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707495","type":"journal-article","created":{"date-parts":[[2007,10,8]],"date-time":"2007-10-08T09:51:19Z","timestamp":1191837079000},"page":"1111-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Agonist\u2010dependent cannabinoid receptor signalling in human trabecular meshwork cells"],"prefix":"10.1111","volume":"152","author":[{"given":"B 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