Activation of adrenal medulla adenylate cylase and catecholamine secretion

The beta-adrenergic agonist, salbutamol, cAMP and theophylline induced secretion of catecholamines (CA) from rat adrenal medulla, incubated in vitro in calcium-free Locke's solution. Beta-adrenergic antagonists inhibited the CA secretion induced by betaadrenergic agonists. The beta₂-antagonist, H35/25, was more effective than the beta₁-antagonist, practolol. Salbutamol augmented the release of CA induced by ouabain or by K-free medium in the presence of calcium. Propranolol partially inhibited the release of CA induced under these conditions, as well as that caused by acetylcholine. Adenylate cyclase activity in a membrane preparation from bovine adrenal medulla was enhanced in decreasing order, by the following catecholamines: isoprenaline > salbutamol > adrenaline > dopamine > noradrenaline. Phenylephrine and tyramine had no effect. The activation of adrenal medullary adenylate cyclase was inhibited by beta-adrenergic antagonists: H 35/25 (a beta₂-antagonist) was more effective than practolol, a beta₁-antagonist. The concentrations of salbutamol and of beta-adrenergic antagonists which activated and blocked, respectively, adenylate cyclase, fit the doses which increased and inhibited, respectively, CA secretion from adrenal medulla in vitro. It is suggested that beta-adrenergic stimulation in the adrenal medulla enhances CA release through an increase of cAMP and that this mechanism may be effective under conditions of intensive physiological stimulation in vivo. Other functions (synthesis of CA, synthesis of tyrosine hydroxylase) may depend on activation of adenylate cyclase in adrenal medulla by beta-adrenoceptors.