Abstract

Isolated cat adrenal glands were perfused in situ with Locke’s solution. The addition of synthetic adrenocorticotropin (0.4-400 µunits/ml) to the perfusion solution for 40 min caused a sustained rise in both tissue adenosine cyclic 3',5'-phosphate levels and corticosteroid release. After a 5-min exposure to ACTH, tissue cyclic AMP levels fell to control values within 30 min, while corticosteroid release was still near maximum. Theophylline increased both basal and ACTH-stimulated tissue cyclic AMP levels but did not further enhance corticosteroid release. Perfusion with calcium-free or potassium-free Locke's solution increased tissue cyclic AMP levels 3-6 fold but did not augment steroid output. Under these ion-deficient conditions, ACTH produced only a very small additional increment in tissue cyclic AMP concentrations but caused a marked increase in steroid release. The addition of cyclic AMP or its dibutyryl derivative to the perfusion solution for up to 30 min did not increase corticoid output. Cyclic AMP was detected in the adrenal perfusate, and its rate of release was augmented by ACTH and by calcium deprivation. These observations are discussed in light of the concept that an increase in tissue cyclic AMP is not sufficient to trigger steroid release, but that a redistribution of cell calcium produced by ACTH is also required.