Inhibitory effect of the kinase inhibitor chelerythrine on acetylcholine-induced current in PC12 cells.

In order to analyze the effect of protein kinase C(PKC) on nicotinic acetylcholine receptor in pheochromocytoma (PC12) cells by the whole-cell clamp technique, chelerythrine, a well-known inhibitor of PKC, was used to investigate the influence of PKC on acetylcholine (ACh)-induced current. When cells were preincubated with chelerythrine (0.1-10 microM) for 5 min, an inhibitory effect of chelerythrine on the peak of ACh-induced current was found. This effect was concentration-dependent, voltage-independent, and time-dependent within 1-6 min and reversible. However, intracellular dialysis with 0.1-5 microM PKCI 19-31, a specific pseudosubstrate PKC inhibitor, did not affect the inhibitory effect of chelerythrine. These results suggest that chelerythrine has an inhibitory effect on ACh-induced current in PC12 cells and that this effect is independent of its inhibition on PKC, may represent a new pharmacological effect of chelerythrine, and is mediated by an alternative mechanism. Copyright 1999 Academic Press.