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  • Title: The role of protein kinase C in nicotinic responses of bovine chromaffin cells.
    Author: Loneragan K, Cheah TB, Bunn SJ, Marley PD.
    Journal: Eur J Pharmacol; 1996 Sep 05; 311(1):87-94. PubMed ID: 8884241.
    Abstract:
    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.
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