Phorbol esters increase adenylate cyclase activity and stability in pituitary membranes.
In this report, we demonstrate that calcium and phorbol esters enhance cAMP production in GH4C1 cell homogenates. The mechanism for this is a reduction in the rate of decay of adenylate cyclase activity over the course of the assay. Purified protein kinase C can reconstitute calcium- and phorbol ester-dependent adenylate cyclase. Phorbol ester-activated protein kinase C increases both the initial rate of cAMP synthesis and reduces the time-dependent decay of adenylate cyclase activity in membrane preparations. The rate of cAMP production is fit to an equation derived from a model which assumes that adenylate cyclase initially exists in a high activity state which decays exponentially into a low activity state. We suggest that protein kinase C can both prevent the decay of the high activity state and convert the low activity state into the high activity state.
Summers
S T
ST
Department of Physiology, University of Virginia, Charlottesville 22908.
Walker
J M
JM
Sando
J J
JJ
Cronin
M J
MJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium