Effects of prostaglandin E2 on adenylate cyclase activity and lipolysis in human adipose tissue

To elucidate the mechanisms of prostaglandin action in human adipose tissue the effects of prostaglandin E2 on isoproterenol-stimulated lipolysis in intact human fat cells and on adenylate cyclase activity of fat-cell ghosts were compared. In intact fat cells prostaglandin E2 caused a dose-dependent inhibition of isoproterenol -stimulated lipolysis which has a maximum of about 40 per cent; half maximal effects were observed at approximately 30 nmol/l prostaglandin E2. In broken cell preparation prostaglandin E2 displayed biphasic effects on adenylate cyclase activity with inhibition occurring in the nanomolar concentration range and stimulation at prostaglandin E2-concentrations above 1 mumol/l. The inhibitory component of prostaglandin E2-action was critically dependent on relatively high concentrations of GTP (greater than 1 mumol/l) and was augmented by sodium ions. The inhibitory component of prostaglandin E2-action on adenylate cyclase reflected the antilipolytic effects of this C-20 fatty acid in intact fat cells with respect to the effective concentration range and degree of inhibition suggesting that the antilipolytic effects of prostaglandins are in fact mediated via inhibition of human fat-cell adenylate cyclase.