Phorbol esters induce two distinct changes in GH3 pituitary cell adenylate cyclase activity.
Phorbol esters alter cyclic AMP levels in a number of tissues, including the anterior pituitary. We report that membrane preparations from GH3 cells exposed to phorbol esters exhibit decreased vasoactive intestinal peptide (VIP)-stimulated and enhanced forskolin-stimulated adenylate cyclase activity. The responsiveness of adenylate cyclase activity to NaF, guanylyl-imidodiphosphate, and Mn2+ was also reduced by phorbol ester treatment. The ability of somatostatin to inhibit forskolin-stimulated adenylate cyclase activity was reduced while phorbol ester exposure had no apparent effect on somatostatin inhibition of VIP-stimulated adenylate cyclase activity. We suggest that protein kinase C alters at least two distinct components of the adenylate cyclase system. One modification disrupts hormone receptor-Gs interaction (lowering VIP efficacy) and the second perturbation augments the activity of the adenylate cyclase catalytic subunit.
Summers
S T
ST
Department of Physiology, University of Virginia School of Medicine, Charlottesville 22908.
Cronin
M J
MJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D014660:Vasoactive Intestinal Peptide; D008345:Manganese; D012969:Sodium Fluoride; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate