Control of adenylate cyclase from secretory vesicle membranes by β 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 l isoproterenol and l 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 l propranolol, a specific β antagonist, but propranolol by itself had no effect on adenylate cyclase activity. The data indicate that the secretory vesicle membrane has β adrenergic receptors coupled to the adenylate cyclase. Propranolol was also found to block the NGF induced inhibition of cyclase. The authors conclude that the granule membrane has β adrenergic receptors as well as NGF reactive sites, and that the two may be functionally linked.