High affinity binding of (/sup 3/H)cocaine to rat liver microsomes
)/sup 3/H)cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in (/sup 3/H)cocaine binding. On the other hand, chronic administration of cocaine reduced (/sup 3/H)cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of (/sup 3/H)cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced (/sup 3/H)cocaine binding to liver with a different rank order of potency than their displacement of (/sup 3/H)cocaine binding to striatum. This high affinity (/sup 3/H)cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity
- Research Organization:
- Univ. of Maryland School of Medicine, Baltimore (USA)
- OSTI ID:
- 5175803
- Journal Information:
- Life Sci.; (United States), Vol. 42:17
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
COCAINE
BIOCHEMICAL REACTION KINETICS
MIXED-FUNCTION OXIDASES
ENZYME INDUCTION
AFFINITY
CATIONS
LIVER
MICROSOMES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHARGED PARTICLES
DIGESTIVE SYSTEM
DRUGS
ENZYMES
GENE REGULATION
GLANDS
IONS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques