The role of protein kinase C in nicotinic responses of bovine chromaffin cells.
The effects of the protein kinase C inhibitor CGP 41251 (31-benzoyl-staurosporine) on nicotinic responses of cultured bovine adrenal chromaffin cells have been investigated. CGP 41251 inhibited tyrosine hydroxylase activation by phorbol 12,13-dibutyrate, with an IC50 of < 0.3 microM and complete inhibition at 1 microM. In contrast, it had little effect on nicotine-stimulated tyrosine hydroxylase activity up to 1 microM, and did not fully inhibit it even at 10 microM. From 1 to 10 microM, CGP 41251 caused a similar concentration-dependent inhibition of tyrosine hydroxylase activity stimulated by nicotine, K+, forskolin and 8-Br-cyclic AMP. CGP 42700 (19,31-dibenzoyl-staurosporine), a structural analogue of CGP 41251 that lacks activity as a protein kinase C inhibitor, had no effect on tyrosine hydroxylase activity stimulated by any of the agonists. CGP 41251 had no effect on catecholamine secretion induced by nicotine. The results suggest phorbol ester-sensitive protein kinase C isozymes do not play a major role in nicotinic stimulation of tyrosine hydroxylase activity or catecholamine secretion in chromaffin cells.
Loneragan
K
K
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Cheah
T B
TB
Bunn
S J
SJ
Marley
P D
PD
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D004791:Enzyme Inhibitors; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D015240:Phorbol 12,13-Dibutyrate; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin