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Title: Distinction between high-affinity (/sup 3/H)phencyclidine binding sites and muscarinic receptors in guinea-pig ileum muscle

Journal Article · · J. Pharmacol. Exp. Ther.; (United States)
OSTI ID:6729243

(/sup 3/H)Phencyclidine ((/sup 3/H)PCP) binding was studied in guinea-pig ileum muscle membranes. Specific binding of (/sup 3/H)PCP was time dependent, reversible and saturable, with an equilibrium dissociation constant of 154 nM and maximum binding of 12.9 pmol/mg of protein at pH 9. Its pH dependency suggests that the un-ionized PCP is the pharmacologically active form. The binding site was on a protein which was sensitive to heat, proteolytic enzymes and the carboxylic group reagent dicyclohexylcarbodiimide, but insensitive to phospholipase A and C, concanavalin A, dithiothreitol and N-ethylmaleimide. Specific (/sup 3/H)PCP binding was displaced effectively by several PCP analogs and Ca/sup + +/ channel antagonists including verapamil, to which these sites had a high affinity. These high-affinity PCP-binding sites were found at a much higher concentration in the same membrane preparation than muscarinic receptor sites identified by their specific binding of (/sup 3/H)quinuclidinyl benzilate. PCP bound to both sites, but with a lower affinity to the muscarinic receptor sites. The PCP and muscarinic receptor sites differed in their sensitivities to pH and drug specifities.

Research Organization:
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore
OSTI ID:
6729243
Journal Information:
J. Pharmacol. Exp. Ther.; (United States), Vol. 229:2
Country of Publication:
United States
Language:
English