Distinct muscarinic receptors and signal transduction pathways in gallbladder muscle. J Pharmacol Exp Ther 273: 650–655

Acetylcholine (ACh) caused a dose-dependent contraction of rine (the protein kinase C inhibitors) by 64%, 75 % and 77%, gallbladder muscle cells in either a normal (1.9 mM) Ca2, respectively. In contrast, in the zero-Ca2 medium, p-flouro-zero-Ca2 or 4 mM Sr2#{247}medium, with a maximal contraction hexahydro-sila-difenidol dose-dependently inhibited ACh-in-about 21 ± 1 % at 1 0_6 M. Pirenzepine, methoctramine and duced contraction and shifted the ACh dose-response curve to p-flouro-hexahydro-sila-difenidol (the Ml, M2 and M3 antago- the right. The action of ACh was further blocked by 10_6 M fist, respectively) alone had no inhibitory effect on ACh-in- U-73122 (phospholipase C inhibitor) and iO M CGS 9343B duced contraction in normal Ca2 medium, which was blocked (calmodulin antagonist) by 95 % and 77%, respectively. In con-by the combination of methoctramine and p-F-HHSiD. In the 4 clusion, ACh contracts the gallbladder muscle by stimulating mM Sr medium, methoctramine dose dependently inhibited the M2 and M3 muscarinic receptors. The M2 receptors are ACh-induced contraction and shifted the ACh dose-response linked to Ca2 influx, activation of phospholipase D and protein curve to the right. The contraction induced by ACh was further kinase C-dependent pathway, whereas the M3 receptors are blocked by 1 0- M propranolol (phosphatidic acid phosphohy- preferentially associated with the activation of phospholipase drolase inhibitor that prevents the production of diacylglycerol C, intracellular Ca2 release and calmodulin-dependent path-from phospholipase D activation), i05 M H-7 and cheleryth- way