Muscarinic receptor subtypes mediating catecholamine secretion and increase in intracellular Ca2+ concentration in adrenal chromaffin cells of the guinea pig.

Muscarinic receptor subtypes mediating catecholamine secretion and increase in the intracellular concentration of Ca2+ ([Ca2+]i) were examined using muscarinic agonists and antagonists in dispersed adrenal chromaffin cells of the guinea pig. All muscarinic agonists (1-1,000 microM) tested caused increases in adrenaline secretion in a dose-dependent manner. Muscarine and methacholine were more effective than bethanechol, oxotremorine and pilocarpine. Muscarine and oxotremorine caused a small increase in adrenaline secretion even in the absence of extracellular Ca2+. Both 4-DAMP (0.1 microM) and pirenzepine (0.1 microM), but not methoctramine (0.1 microM), shifted the dose-response curve for muscarine-induced adrenaline secretion to the right. These muscarinic agonists also caused increase in [Ca2+]i in the presence of extracellular Ca2+. Muscarine-induced [Ca2+]i rises were reduced, but not abolished, by removal of extracellular Ca2+. These results suggest that catecholamine secretion induced by muscarinic agonists is mediated through M1, or M1 and M3 muscarinic receptor subtypes in adrenal chromaffin cells of the guinea pig.