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.
Okumura
T
T
Department of Medical Chemistry, Kansai Medical School, Osaka, Japan.
Sago
T
T
Saito
K
K
D000367:Age Factors; D000818:Animals; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D006728:Hormones / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D037342:Pertussis Toxin; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
D002250:Carbon Radioisotopes; D006728:Hormones; D008112:Liver Glycogen; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D010566:Virulence Factors, Bordetella; C017244:16,16-dimethylprostaglandin E; D037342:Pertussis Toxin