Phorbol ester-induced upregulation of angiotensin II receptors in neuronal cultures is potentiated by a calcium ionophore.
Previous studies have suggested that protein kinase C is important in the regulation of angiotensin II receptors in neuronal cultures, because the C-kinase agonists, phorbol esters, are able to increase the number of these receptors. In the present study, we have further investigated the role of protein kinase C in angiotensin II receptor regulation. This enzyme is calcium dependent, and so we investigated the effects of A23187, a calcium ionophore, on phorbol ester-stimulated and basal angiotensin II receptor regulation. A23187, at concentrations that increased 45Ca2+ influx, caused a dose-dependent potentiation of phorbol-12-myristate-13-acetate (TPA)-stimulated upregulation of angiotensin II receptors. This potentiation by A23187 was a further increase in angiotensin II receptor number and was abolished in calcium-free medium. In the absence of TPA, A23187 caused a decrease in angiotensin II receptor number, an effect not observed in calcium-free medium. The results suggest at least two pathways for angiotensin II receptor regulation in neuronal cells: (a) by calcium-dependent protein kinase C and (b) via an influx of calcium into the cell.
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001152:Arsenicals; D002132:Calcium Radioisotopes; D011945:Receptors, Angiotensin; C029341:oxophenylarsine; D000804:Angiotensin II; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate