Protein kinase C activation enhances cAMP accumulation in Swiss 3T3 cells: inhibition by pertussis toxin.
Addition of phorbol 12,13-dibutyrate (PBt2) in the presence of forskolin or cholera toxin caused marked (6- to 8-fold) and rapid accumulation of cAMP in Swiss 3T3 cells. The effect of PBt2 is mediated by protein kinase C because the synthetic diacylglycerol 1-oleoyl-2 acetylglycerol substitutes for PBt2 in enhancing cAMP accumulation and because the enhancing effect of either PBt2 or 1-oleoyl-2-acetylglycerol was prevented by down-regulation of protein kinase C. Vasopressin, which activates protein kinase C but does not directly affect adenylate cyclase in 3T3 cells, also enhanced cAMP accumulation in cells treated with cholera toxin or forskolin. This effect was abolished by down-regulation of protein kinase C. Treatment with pertussis toxin blocked the enhancing effect of PBt2 in a concentration- and time-dependent manner. Pertussis toxin neither prevented protein kinase C activation by PBt2 nor other biologic responses elicited by PBt2. The results presented here suggest an unusual function for a pertussis toxin substrate--namely, coupling protein kinase C activation to cAMP production.
D037361:Adenylate Cyclase Toxin; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D002273:Carcinogens; D004075:Diglycerides; D010703:Phorbol Esters; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; C038237:1-oleoyl-2-acetylglycerol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000527:Alprostadil