Mechanism of choline-induced secretion of catecholamines from the cat adrenal medulla: involvement of nicotinic receptor.

Cat adrenal glands were retrogradely perfused in vitro with modified Locke's medium and the mechanism of catecholamine (CA) secretion induced by choline was investigated. Choline-induced secretion of CA was accompanied by release of dopamine-beta-hydroxylase, but not by that of phenylethanolamine-N-methyl transferase, indicating that an exocytotic mechanism is involved in the secretion. Choline failed to induce the secretion of CA when Ca was absent from the perfusion solution. On the other hand, secretion increased when the concentration of Ca2+ in the perfusion medium was raised to 10 mM. Stimulation of secretion by choline was observed from a concentration of 1 mM, and half-maximal secretion occurred at about 10 mM. The stimulatory action was weaker than that of acetylcholine(ACh); the effect of 100 mM choline was approximately equal to that of 0.02 mM ACh. Secretion induced by a low concentration of choline was abolished by a nicotinic blocker, hexamethonium, while the response to choline at a concentration higher than 130 mM was only partially inhibited by cholinergic antagonists. The effects of choline and a low concentration of ACh were additive. On the other hand, 100 mM choline inhibited the response to a supramaximal concentration of ACh(0.5 mM), suggesting that ACh and choline stimulate the same nicotinic receptor. It is concluded that choline acts partially as a nicotinic agonist and that a concentration higher than 130 mM causes secretion by a mechanism additional to nicotinic receptor activation.