Stimulation-evoked cyclic nucleotides efflux from isolated perfused dog adrenals and possible involvement of calcium

Nicotine and muscarine caused the transient increase in cAMP and cGMP efflux from dog adrenal glands followed by a small but lasting increase in the nucleotide efflux. The initial increase preceded catecholamine (CA) release and the latter slowly developed. Nicotine and muscarine caused the maximal increase of cAMP and cGMP levels in adrenal medulla 15 sec after the treatment, and these effects were antagonized by hexamethonium and atropine, respectively. Hexamethonium in combination with atropine, verapamil and an omission of Ca2+ in the medium prevented ACh from producing the increase in cyclic nucleotide efflux and CA release. Reintroduction of Ca2+ (1.3 mM) in fluid after perfusion with Ca2+ and Mg2+-free fluid caused the transient increase in cyclic nucleotide efflux and CA release. Adenylate cyclase activity in adrenal medulla was activated by Ca2+. These results may suggest that cAMP formation was increased by activation of adenylate cyclase as a result of increased influx of Ca2+ when adrenal medulla were stimulated.