Effects of staurosporine on ACTH-mediated stimulation of aldosterone production.
Incubation of rat adrenal glomerulosa cells with low concentrations (up to 50 nM) of the protein kinase (PKC) inhibitor staurosporine (ST) inhibited aldosterone (ALDO) and cyclic AMP (cAMP) production stimulated by adrenocorticotropic hormone (ACTH) and cholera toxin. Only higher concentrations (1.6 microM) of staurosporine inhibited dibutyryl-cAMP- and forskolin-induced stimulation of aldosterone production. cAMP levels were increased only with low concentrations of the PKC inhibitor. This latter increase was avoided by treatment with a maximal concentration of isobutylmethylxanthine (MIX). Our results suggest that: (1) second messengers other than cAMP are involved in ACTH action; (2) staurosporine inhibits different kinases involved in ACTH action in a dose-dependent manner; (3) the protein kinase inhibited by high concentrations of staurosporine appears to be the cAMP-dependent kinase, PKA; and (4) the protein kinase inhibited by low concentrations of staurosporine remains to be identified. This latter species is suggested as being involved in mediating ACTH-induced activation of Gs.
Pecci
A
A
Departamento de Química Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Romero
D G
DG
Gomez-Sanchez
C E
CE
Lantos
C P
CP
Cozza
E N
EN
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003366:Cosyntropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism*
D010446:Peptide Fragments; D003366:Cosyntropin; D005576:Colforsin; C011393:ACTH (1-10); C034016:ACTH (11-24); D000450:Aldosterone; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D019311:Staurosporine