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

Journal Article · Tue May 01 04:00:00 EDT 1984 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6729243

El-Fakahany, E E; Triggle, D J; Eldefrawi, A T; Eldefrawi, M E

(/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), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 229:2; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
551001 -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AGGLUTININS
ANESTHETICS
ANTIBODIES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLESTERASES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CONCANAVALIN
DIGESTIVE SYSTEM
DRUG ABUSE
DRUGS
ENZYMES
ESTERASES
GASTROINTESTINAL TRACT
HEMAGGLUTININS
HYDROLASES
INTESTINES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPASE
ORGANS
REACTION KINETICS
RECEPTORS
SMALL INTESTINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS