Stimulation of Release of Adrenal Catecholamine by Adenosine 3′:5′-Cyclic Monophosphate and Theophylline in the Absence of Extracellular Ca2+
Abstract
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 Ca2+-free Locke's solution for 30-180 min rapidly lost their responsiveness to KCl or nicotine. In contrast, exposure to Ca2+-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 Ca2+ to release adrenal catecholamines. They may act by translocating intracellular bound Ca2+ or by a mechanism independent of calcium.
