Phorbol esters enhance basal and stimulated adenylate cyclase activity in a pituitary cell line.
We reported in anterior pituitary cells that hormone stimulation of cyclic AMP levels is amplified by agents that activate protein kinase C (e.g., phorbol esters). We utilized the 235-1 pituitary cell line to explore the mechanism of this response. PGE1- and forskolin-stimulated cyclic AMP accumulation and adenylate cyclase activity are enhanced by exposing viable cells to phorbol esters. Adenylate cyclase activity in the presence of PGE1 demonstrated a biphasic stimulatory, then inhibitory response to increasing GTP concentrations; phorbol esters attenuated this inhibition. These data support the hypothesis that protein kinase C can covalently change the functional state of the adenylate cyclase holoenzyme, amplifying its response to certain hormones.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004357:Drug Synergism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D010902:Pituitary Gland / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D010703:Phorbol Esters; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil