Inhibition of the stimulatory effect of adrenaline and prostaglandin E1 on the human fat cell adenylate cyclase by adenosine

Abstract

Adenosine is known to modulate adenylate cyclase activity in a variety of tissues. We have tested the effects of adenosine on basal activity and the catecholamine- or prostaglandin E1-stimulated activity of the human fat cell adenylate cyclase. Adenosine caused a dose-dependent inhibition of basal enzyme activity as well as of adrenaline-and prostaglandin E1-stimulated rates of 3',5'-cyclic AMP accumulation. The adenosine-induced inhibition was specific since other nucleosides or their respective nitrogenous parent bases, with the exception of adenine, failed to mimic the action of adenosine. In addition, the adenosine-induced inhibition could be reversed by inclusion of adenosine deaminase. The results are compatible with the concept of adenosine acting as an inhibitor of lipolysis at the level of the membrane-bound adenylate cyclase. They show that this nucleoside can also inhibit the prostaglandin E1-induced stimulation of the human fat cell adenylate cyclase thereby suggesting that the effects of adenosine and prostaglandins might be antagonistic under conditions where prostaglandins act as stimulators of lipolysis.