Specific Gq protein involvement in muscarinic M3 receptor-induced phosphatidylinositol hydrolysis and Ca2+ release in mouse duodenal myocytes

British Journal of Pharmacology
J L MorelJ Mironneau

Abstract

1. Cytosolic Ca2+ concentration ([Ca2+]i) during exposure to acetylcholine or caffeine was measured in mouse duodenal myocytes loaded with fura-2. Acetylcholine evoked a transient increase in [Ca2+]i followed by a sustained rise which was rapidly terminated after drug removal. Although L-type Ca2+ currents participated in the global Ca2+ response induced by acetylcholine, the initial peak in [Ca2+]i was mainly due to release of Ca2+ from intracellular stores. 2. Atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, a muscarinic M3 antagonist), pirenzepine (a muscarinic M1 antagonist), methoctramine and gallamine (muscarinic M2 antagonists) inhibited the acetylcholine-induced Ca2+ release, with a high affinity for 4-DAMP and atropine and a low affinity for the other antagonists. Selective protection of muscarinic M2 receptors with methoctramine during 4-DAMP mustard alkylation of muscarinic M3 receptors provided no evidence for muscarinic M2 receptor-activated [Ca2+]i increase. 3. Acetylcholine-induced Ca2+ release was blocked by intracellular dialysis with a patch pipette containing either heparin or an anti-phosphatidylinositol antibody and by external application of U73122 (a phospholipase C inhibitor). 4. Acetylcholine-ind...Continue Reading

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Citations

Jan 15, 1999·Pharmacology & Therapeutics·J Wess
May 1, 1998·Trends in Cardiovascular Medicine·J Mironneau, N Macrez
Apr 28, 2001·British Journal of Pharmacology·M W HollmannM E Durieux
Apr 1, 2000·Clinical and Experimental Pharmacology & Physiology·M KuritaH Nakanishi
Sep 2, 2008·Canadian Journal of Physiology and Pharmacology·Nicolas FritzJean-Luc Morel
Jan 29, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas A WhiteTimothy F Walseth
May 14, 2004·The Journal of Biological Chemistry·Hong ShiZhiguo Wang
Feb 27, 2004·The Journal of Biological Chemistry·Jean-Luc MorelJean Mironneau
Aug 1, 2006·European Journal of Pharmacology·Shigeyoshi HonmaNorimichi Nakahata

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