Phencyclidine inhibition of the acetylcholine receptor: measurement of cation flux in a sympathetic neuronal cell line using 22Na+ and spectroscopic detection of Cs+.
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 mM carbamoylcholine the rate of the receptor-controlled influx of 22Na+ is reduced by a factor of 2 by 0.7 microM 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 receptor-controlled 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.
D000818:Animals; D002460:Cell Line; D002586:Cesium / Q000032:analysis*; D002999:Clone Cells; D007700:Kinetics; D009474:Neurons / Q000378:metabolism*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism
D011950:Receptors, Cholinergic; D002586:Cesium; D012964:Sodium; D010622:Phencyclidine