Analysis of the role of cyclic adenosine 3',5'-monophosphate in catecholamine release.

1. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels and catecholamine release were measured in cat adrenal glands perfused in situ with Locke solution.2. Cyclic AMP was present in the medulla in an amount which represented approximately one fifth of that present in the cortex.3. Perfusion with acetylcholine (ACh) or nicotine increased cyclic AMP both in the intact adrenal and in the perfusate. The time course of the changes in tissue cyclic AMP during stimulation was out of phase with the time course of catecholamine release. Maximal increases in cyclic AMP were not manifest until after 8 min of exposure to the secretogogue, whereas maximal rates of secretion occurred during the first minute.4. Theophylline (0.5 mM) increased basal and stimulated adrenal cyclic AMP levels, but did not potentiate the secretory response to ACh or nicotine.5. Perfusion with cyclic AMP or its dibutyryl derivative (0.2-4 mM) failed to effect a consistent or significant increase in the rate of catecholamine release and was unable to potentiate the secretory response to a submaximal concentration of ACh or calcium.6. The results suggest that, unlike calcium, cyclic AMP is not a direct mediator of medullary secretion.