Effect of protein kinase inhibitors on ACTH-stimulated aldosterone production in rat zona glomerulosa cells.
In order to obtain further evidence for the involvement of protein kinases in the short-term ACTH-stimulated aldosterone synthesis in rat zona glomerulosa cells, the effects of three different compounds with protein kinase inhibitory properties were investigated. Staurosporine, H-7 and trifluoperazine inhibited ACTH-stimulated aldosterone release in a dose-dependent manner. While the inhibitory effect of H-7 was reversible upon washing of the cells with inhibitor-free medium, the inhibition was maintained in cells treated with staurosporine or trifluoperazine. In contrast to the stimulated production, basal release of aldosterone even at the highest drug concentrations tested was not completely inhibited. We thus conclude that protein kinases may play a crucial role in short-term ACTH-stimulated aldosterone production in rat glomerulosa cells.
Kurscheid-Reich
D
D
Yale University, School of Medicine, Dept. Internal Medicine, New Haven, CT 06510-8056.
Hegemann
L
L
Wohlfeil
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D014268:Trifluoperazine / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D014268:Trifluoperazine; D000450:Aldosterone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000324:Adrenocorticotropic Hormone; D019311:Staurosporine