Characterization of a high affinity cocaine binding site in rat brain
Binding of (/sup 3/H)cocaine to synaptic membranes from whole rat brain was reversible and saturable. Nonlinear regression analysis of binding isotherms indicated two binding affinities: one with k/sub d/ = 16 nM, B/sub max/ = 0.65 pmoles/mg protein and the other with K/sub d/ = 660 nM, B/sub max/ = 5.1 pmoles/mg protein. The high-affinity binding of (/sup 3/H)cocaine was sensitive to the actions of trypsin and chymotrypsin but not carboxypeptidase, and was eliminated by exposure of the membranes to 95/sup 0/C for 5 min. Specific binding at 2 nM was higher at pH 8.8 than at pH 7.0. Binding of (/sup 3/H)cocaine (15 nM) was inhibited by increasing concentrations of Na/sup +/ ions. Several cocaine analogues, neurotransmitter uptake inhibitors and local anesthetics displaced specific (/sup 3/H)cocaine binding at 2 nM with various potencies. The cocaine analogue (-)-norcocaine was the most potent (IC/sub 50/ = 10 nM), while the local anesthetic tetracaine was the least potent in inhibiting (/sup 3/H)cocaine binding. Several biogenic amine uptake inhibitors, including tricyclic antidepressants and phencyclidine, had IC/sub 50/ values below ..mu..M concentrations.
- Research Organization:
- Univ. of Maryland School of Medicine, Baltimore
- OSTI ID:
- 7119424
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
COCAINE
BIOCHEMICAL REACTION KINETICS
RECEPTORS
AFFINITY
BRAIN
CELL MEMBRANES
NERVE CELLS
RATS
REGRESSION ANALYSIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
ANESTHETICS
ANIMAL CELLS
ANIMALS
ANTIDEPRESSANTS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATHEMATICS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
SOMATIC CELLS
STATISTICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques