Muscarinic acetylcholine receptor compounds alter net Ca2+ flux and contractility in an invertebrate smooth muscle.

Responses of a holothurian smooth muscle to a range of muscarinic (M(1) to M(5)) acetylcholine receptor (mAChR) agonists and antagonists were surveyed using calcium (Ca(2+))-selective electrodes and a mechanical recording technique. Most of the mAChR agonists and antagonists tested increased both contractility and net Ca(2+) efflux, with M(1)-specific agents like oxotremorine M being the most potent in their action. To investigate the possible sources of Ca(2+) used during mAChR activation, agents that disrupt intracellular Ca(2+) ion sequestration [cyclopiazonic acid (CPA), caffeine, ryanodine], the phosphoinositide signaling pathway [lithium chloride (LiCl)], and L-type Ca(2+) channels (diltiazem and verapamil) were used to challenge contractions induced by oxotremorine M. These contractions were blocked by treatment with CPA, caffeine, LiCl, and by channel blockers, diltiazem and verapamil, but were unaltered by ryanodine. Our data suggest that this smooth muscle had an M(1,3,5)-like receptor that was associated with the phosphoinositide signaling pathway that relied on intracellular Ca(2+) stores, but secondarily used extracellular Ca(2+) via the opening of L-type channels.