title: Angiotensin II potentiates agonist-induced 3',5'-cyclic adenosine monophosphate production by cultured bovine adrenal cells through protein kinase C and calmodulin pathways.
abstract: Interactions between signal transducing systems may be important in the integrated control of cellular processes in basal and hormonally regulated cells. The cultured bovine adrenal fasciculata cell provides a model to study the interactions between the cAMP and calcium-sensitive phospholipid dependent protein kinase C. In this study, angiotensin II (A-II) and phorbol ester (PMA) potentiated the stimulatory actions of ACTH in a dose-dependent manner on cAMP production. At maximal concentrations, A-II and PMA also potentiated the effects of cholera toxin and forskolin on cAMP production. Both staurosporine, a protein kinase C inhibitor, and desensitization of protein kinase C by a 24-h pretreatment with PMA blunted the effect of PMA, but only partially inhibited (34%) the effect of A-II. Neither nifedipine, a specific calcium channel antagonist, nor pretreatment of cells with pertussis toxin modified the amplifying effects of A-II or PMA. In contrast, trifluoperazine, a calmodulin inhibitor, reduced the potentiating effect of A-II by about 35%, but association with staurosporine blunted its effects. Moreover, the steroidogenic effects of ACTH plus A-II were more than additive, but this synergism was blunted in the presence of both inhibitors. In conclusion, PMA and A-II potentiated agonist-induced cAMP production by bovine adrenal fasciculata cells. The data suggest that the effects of PMA were mediated exclusively by protein kinase C, whereas those of A-II were mediated by both protein kinase C and calmodulin.
authors.affiliation: INSERM U 307, Hôpital Debrousse, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Langlois
authors.forename: M
authors.initials: M
authors.lastname: Bégeot
authors.forename: M C
authors.initials: MC
authors.lastname: Berthelon
authors.forename: C
authors.initials: C
authors.lastname: Jaillard
authors.forename: J M
authors.initials: JM
authors.lastname: Saez
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002147:Calmodulin / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D006854:Hydrocortisone / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D015220:Calcium Channels; D002147:Calmodulin; D000804:Angiotensin II; D005576:Colforsin; D014268:Trifluoperazine; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone