Sensitization of adrenocortical cell adenylate cyclase activity to ACTH by angiotensin II and activators of protein kinase C.
Exposure of bovine adrenocortical cells to optimal concentrations of angiotensin II (A II) resulted in an almost 2-fold enhancement of cellular cAMP accumulation in response to steroidogenic concentrations of ACTH. This effect was dose-dependent and transient, with a maximum after 4-6 min of treatment with A II. Activators of protein kinase C such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 1,2-dioctanoyl-sn-glycerol mimicked that effect in a sustained fashion. The ACTH-sensitized state of the adrenocortical adenylate cyclase system induced by TPA exhibited also an enhanced response to forskolin. On the other hand, previous treatment of the cells by pertussis toxin suppressed any further effect of TPA. It is suggested that, following A II exposure, the Gi inhibitory components of the adrenocortical cell adenylate cyclase system may be inactivated, leading to increased response to ACTH. This process may involve protein kinase C activation, subsequent to intracellular generation of lipidic messengers resulting from accelerated phosphoinositide breakdown induced by angiotensin.
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D004075:Diglycerides; D010566:Virulence Factors, Bordetella; C044295:1,2-dioctanoylglycerol; D000804:Angiotensin II; D005576:Colforsin; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate