Pertussis toxin blocks an inhibition of hormone-stimulated glycogenolysis by prostaglandin E2 and its analogue in cultured hepatocytes.

Prostaglandin E2 (PGE2) and 16,16-dimethyl PGE2 were found to inhibit a hepatic glycogenolysis stimulated by epinephrine in the presence of propranolol (alpha 1-adrenergic response), isoproterenol (beta-adrenergic response) and glucagon in primary cultures of rat hepatocytes. The inhibitory effects to these stimulations were maximally increased (60-100%) in the cultures on day 2 or 3. Pretreatment of the cultured hepatocytes with pertussis toxin (islet-activating protein) resulted in a complete blockage of the prostaglandin-induced inhibition of glycogenolysis in a dose-dependent manner. Pertussis toxin had no significant effect on the glycogenolysis stimulated by these compounds in the absence of prostaglandin. The data suggest that the hepatic glycogenolysis stimulated by alpha 1- and beta-adrenergic responses and glucagon are modulated by the E series of prostaglandins via pertussis toxin-sensitive guanine nucleotide regulatory protein.