Treatment of primary cultures of calf adrenal glomerulosa cells with adrenocorticotropin (ACTH) and phorbol esters: a comparative study of the effects on aldosterone production and ACTH signaling system.
We studied the mechanism that underlies the desensitization of calf adrenal glomerulosa cells induced by 4 h of ACTH treatment. In control cells, acute ACTH treatment provoked sizeable increases in aldosterone, cAMP, and diacylglycerol, and translocated protein kinase-C from cytosol to membrane. In desensitized cells, acute ACTH effects on aldosterone and cAMP decreased by 25-60%, and diacylglycerol levels and protein kinase-C translocation were persistently stimulated and not substantially affected by further acute ACTH treatment. After 4 h of treatment with 1 microM phorbol 12-myristate 13-acetate (PMA) there were no acute effects of ACTH on the production of aldosterone, cAMP, or diacylglycerol or on protein kinase-C, which was already strongly translocated. These results suggest that ACTH-mediated desensitization of calf adrenal glomerulosa cells may be at least partially mimicked by long term treatment with phorbol esters and could be due to ACTH-induced increases in diacylglycerol-protein kinase-C signaling.
Cozza
E N
EN
Department of Internal Medicine and Biochemistry, University of South Florida, Tampa 33612.
Vila
M C
MC
Acevedo-Duncan
M
M
Farese
R V
RV
Gómez-Sánchez
C E
CE
D000311:Adrenal Glands / Q000166:cytology* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology* / Q000502:physiology; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D005260:Female; D007158:Immunologic Techniques; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate