Inhibition of human fat cell adenylate cyclase mediated via alpha-adrenoceptors.

Abstract

Human adipose tissue contains alpha- as well as beta-adrenoceptor sites mediating antagonistic catecholamine effects on lipolysis. To characterize the mechanisms of catecholamine action in biochemical terms we have studied the effects of the almost pure beta-adrenoceptor agonist isoproterenol and of the mixed adrenergic agonist adrenaline on human fat cell adenylate cyclase in the presence of alpha- and beta-adrenoceptor blocking drugs. In contrast to the almost pure beta-adrenergic agent isoproterenol, the mixed agonist adrenaline, besides its stimulatory action, also had inhibitory effects which became apparent upon complete beta-adrenoceptor blockade using 0.05 mmol/l propranolol. Under these conditions adrenaline caused a dose-dependent inhibition of basal and parathyroid hormone-activated enzymic activity with a maximum of 30-50%, which was dependent on GTP and could be reversed by simultaneous alpha-adrenergic blockade using 5 mumol/l dihydroergotamine or 10 mumol/l phentolamine. These results support the concept of antogonistic alpha- and beta-adrenoceptor sites coexisting as regulatory subunits of the human fat cell adenylate cyclase.