Control of adenylate cyclase from secretory vesicle membranes by beta-adrenergic agents and nerve growth factor.

Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of purified secretory vesicle membranes from the adrenal medulla is inhibited by I-isoproterenol and I-epinephrine, as well as by nerve growth factor (NGF). The effect of these agents was found to be dose-dependent and, in the case of the catecholamines, saturable. NGF was active at concentrations as low as 10(-8) M. Oxidized NGF was only minimally active, and insulin was completely inactive. Neither dopamine nor phenylephrine had activity. Inhibition of cyclase by either isoproterenol or epinephrine was blocked by I-propranolol, a specific beta-antagonist, but propranolol by itself had no effect on adenylate cyclase activity. The data indicate that the secretory vesicle membrane has beta-adrenergic receptors coupled to the adenylate cyclase. Propranolol was also found to block the NGF-induced inhibition of cyclase. We conclude that the granule membrane has beta-adrenergic receptors as well as NGF-reactive sites, and that the two may be functionally linked.