Acetylcholine stimulates steroidogenesis in isolated frog adrenal gland through muscarinic receptors: evidence for a desensitization mechanism

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Abstract
The effect of cholinergic agonists on glucocorticoid and mineralocorticoid production by frog interrenal (adrenal) tissue was studied in vitro by means of continuous perifusion. Acetylcholine, at doses ranging from 1 to 100 μmol/l, stimulated both corticosterone and aldosterone output in a dose-dependent manner, with a half-maximal effective dose of 2·5 μmol/l. Corticosteroid production was also stimulated by muscarine (10 μmol/l). In contrast, neither nicotine nor nicotine bitartrate (1–100 μmol/l) enhanced corticosteroid biosynthesis. The kinetics of the response of adrenal cells to acetylcholine and muscarine were similar to those observed during angiotensin II stimulation. In particular, a significant reduction (20–40%) in the spontaneous level of corticosteroid production was recorded after the initial infusion of muscarinic agents, but no further decrease in the basal level occurred after a second cholinergic administration. The effect of acetylcholine was blocked by the muscarinic receptor antagonist atropine (10 μmol/l). These results indicate that acetylcholine can stimulate frog adrenocortical cells through muscarinic receptors. Repeated 20-min pulses of acetylcholine (50 μmol/l) or muscarine (10 μmol/l), given at one pulse per 130 min, resulted in a marked reduction in the secretory response to the second pulse. No reduction in the stimulatory effect of acetylcholine or muscarine was observed when a 6·5-h interval separated two 20-min infusions of the secretagogue. In contrast with these findings, iterative pulses of the muscarinic agonist pilocarpine (in the range 1–100 μmol/l) did not cause any desensitization. These data show that the neurotransmitter acetylcholine can modulate frog adrenocortical function and suggest that, in addition to more conventional regulators, i.e. ACTH and angiotensin II, the cholinergic endings of the splanchnic nerve might participate in the regulation of corticosteroid secretion, at least under some physiological conditions such as neurogenic stress. J. Endocr. (1987) 113, 339–348