Acceleration of the adipocyte adenylate cyclase turn-off reaction by inhibitory hormonal factors.

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Abstract
.beta.-Adrenergic agonists such as isoproterenol stimulate hamster adipocyte adenylate cyclase by a GTP-dependent process, whereas prostaglandin E1, .alpha.-adrenergic agonists and nicotinic acid inhibit the enzyme by a process also dependent on GTP and amplified by Na ions. The 1st-order rate constant describing the decay of isoproterenol plus GTP-stimulated adenylate cyclase and the modulation of this off rate constant by Na and inhibitory hormonal factors were determined. With 1 .mu.M GTP and 0.2 mM isoproterenol, the off rate constant was 5.0 min-1 at 25.degree. C. Addition of NaCl (100 mM), which increased basal and isoproterenol-stimulated cyclase activities, decreased the rate constant of the hormone-stimulated enzyme to 1.4 min-1. Prostaglandin E1 (10 .mu.M) and nicotinic acid (30 .mu.M), which decreased basal and hormonally stimulated enzyme activities, increased the NaCl-suppressed off rate constant to 6.1 and 6.0 min-1, respectively. Similar data were obtained with 1 mM isoproterenol with MnATP and MgATP as the adenylate cyclase substrate. The turn-on reaction of adipocyte adenylate cyclase, measured with the stable GTP analog 5''-guanylyl imidodiphosphate (30 .mu.M), was accelerated by isoproterenol (1 mM) and NaCl (100 mM). Under all of these conditions, inhibitory hormonal agents did not cause any delay in the turn-on reaction. In hamster adipocyte membranes, inhibitory hormonal factors inhibit adenylate cyclase by increasing the enzyme''s turn-off reaction.