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

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Abstract
Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of purified secretory vesicle membranes from the [bovine] adrenal medulla is inhibited by l-isoproterenol, l-epinephrine, and nerve growth factor (NGF). The effect of these agents was 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 doapmine nor phenylephrine had activity. Inhibition of cyclase by either isoproterenol or epinephrine was blocked by l-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 blocked the NGF-induced inhibition of cyclase. The granule membrane probably has .beta.-adrenergic receptors and NGF-reactive sites; the 2 may be functionally linked.