Inhibitory Effect of Prostaglandins on the Stimulation by Glucagon and Adrenaline of Formation of Cyclic AMP in Rat Hepatocytes

Abstract

Several prostaglandins were found to inhibit hormone-induced cyclic AMP accumulation in suspensions of intact rat hepatocytes. Prostaglandin E1 in concentrations of 0.05--25 micrometers inhibited the cyclic AMP response to glucagon. Maximal inhibition was about 50%. The effect was rapid, being evident within 30 s. Prostaglandins E2, F1 alpha, F2 alpha, A1 and A2 also inhibited the glucagon effect on cyclic AMP in hepatocytes. In cells made highly responsive to adrenaline, by pretreatment of the animals with the carcinogen 2-acetylaminofluorene, and inhibitory effect of prostaglandin E1 was seen also on adrenaline-induced cyclic AMP accumulation. The mechanism of the inhibitory effect of prostaglandins on hormone-stimulated cyclic AMP accumulation was not clarified. Prostaglandin E1 did not inhibit glucagon binding to intact hepatocytes, and so far we have not been able to demonstrate any effect of the prostaglandins on the adenylate cyclase or phosphodiesterase in broken cell preparations. It is concluded that while several previous studies have shown that stimulatory effects of prostaglandins on cyclic AMP are only marginal or lacking in parenchymal liver cells the present data indicate that several prostaglandins exert strong inhibitory interference with hormone-induced cyclic AMP accumulation.