Glucagon facilitates adrenal catecholamine release mediated by nicotinic receptors but not by muscarinic receptors in anesthetized dogs.

Abstract

We examined the effects of glucagon on the release of adrenal catecholamines (CAs) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP), and muscarine in anesthetized dogs. Glucagon and the cholinergic drugs were infused and injected, respectively, into the adrenal gland through the phrenicoabdominal artery. SNS (1 and 3 Hz) or injections of ACh (1.5 and 3 micrograms), DMPP (1 and 2 micrograms), and muscarine (1 and 2 micrograms) produced a frequency- or dose-dependent increase in both epinephrine (EPI) and norepinephrine (NE) output, determined from adrenal venous blood. Glucagon infusion (0.1, 0.3, and 1 microgram/min) enhanced the SNS-, ACh-, and DMPP-induced increases in EPI and NE output in a dose-dependent manner but did not affect the muscarine-induced increases in CA output. The increase in basal CA output induced by the highest dose of glucagon was only slight. Glucagon increased cyclic AMP overflow determined from adrenal venous blood. Our results indicate that glucagon has a facilitatory action on adrenal CA release mediated by nicotinic receptors but not by muscarinic receptors in dogs and suggest that an increase in cyclic AMP production in adrenal medullary cells may be responsible for its selective action.