Stimulation of Release of Adrenal Catecholamine by Adenosine 3′:5′-Cyclic Monophosphate and Theophylline in the Absence of Extracellular Ca 2+

Stimulation of catecholamine release was studied in the isolated adrenal of the cat during retrograde perfusion. Theophylline, adenosine 3':5'-cyclic monophosphate (cyclic AMP), and dibutyryl-cyclic AMP stimulated catecholamine release in adrenal chromaffin tissue; adenosine, 2'-AMP, 3'-AMP, and 5'-AMP were ineffective. Addition of theophylline for 5-15 min had no effect on catecholamine release induced by KCl or nicotine, but it significantly increased the responses to cyclic AMP and its dibutyryl derivative. Glands perfused with Ca(2+)-free Locke's solution for 30-180 min rapidly lost their responsiveness to KCl or nicotine. In contrast, exposure to Ca(2+)-free medium for 180 min had no effect on secretory responses to either the cyclic nucleotides, themselves, or to methylxanthine-induced potentiation of cyclic AMP responses. Thus, dibutyryl-cyclic AMP, cyclic AMP, and theophylline do not require extracellular Ca(2+) to release adrenal catecholamines. They may act by translocating intracellular bound Ca(2+) or by a mechanism independent of calcium.