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.
Shi
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Department of Physiology, Second Military Medical University, Shanghai, 200433, People's Republic of China.
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D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D011978:Receptors, Nicotinic; C016299:chelerythrine; D011493:Protein Kinase C; D000109:Acetylcholine