Phencyclidine inhibition of the acetylcholine receptor: Measurement of cation flux in a sympathetic neuronal cell line using 22Na+ and spectroscopic detection of Cs+

Abstract The site of action of phencyclidine, a powerful and increasingly abused drug, in sympathetic nerve cells has not previously been identified. Here it is demonstrated that phencyclidine is a powerful, noncompetitive inhibitor of the nicotinic acetylcholine receptor in a sympathetic nerve cell line, PC-12. In the presence of 1 m m carbamoylcholine the rate of the receptor-controlled influx of 22 Na + is reduced by a factor of 2 by 0.7 μ m phencyclidine. Increasing concentrations of carbamoylcholine cannot reverse the inhibitory effect of the drug. Both the transmission of electrical signals between nerve cells and the secretion of catecholamines in the PC-12 cell line depend on the receptorcontrolled ion flux. Thus phencyclidine interferes with at least two specific, physiologically important functions of these nerve cells. A new spectroscopic method has been developed to measure cation flux in cells. It is shown that this method can replace measurements of tracer ion flux.