Identification, characterization, and purification of a 65,000 dalton protein in rat brain is photolabeled by nitro-containing benzodiazepines

Miscellaneous · Fri Jan 01 00:00:00 EST 1988

OSTI ID:6828167

Bowling, A C

Benzodiazepines bind to two well-characterized classes of nanomolar-affinity binding sites, the central and the peripheral types. Although these sites appear to mediate many of the effects of these compounds, they cannot account for all of the biochemical and physiologic effects of the benzodiazepines. In this investigation, a protein that is photolabeled by NO{sub 2}-containing benzodiazepines was identified and characterized in rat brain by performing photaffinity labeling experiments with ({sup 3}H)-clonazepam and ({sup 3}H)-flunitrazepam. These experiments demonstrate that this photolabeled protein has a molecular weight of 65,000 daltons. Photolabeling of the protein was saturable, inhibited in a stereoselective manner by benzodiazepine enantiomers, inhibited by therapeutically-relevant concentrations of many different NO{sub 2}-containing benzodiazepines, and was not inhibited by more than 70 non-benzodiazepine compounds. The photolabeled protein is distinct from the central and peripheral sites on the basis of molecular weight, benzodiazepine inhibitory potencies, subcellular localization, and tissue distribution.

• Research Organization: Yale Univ., New Haven, CT (USA)
• OSTI ID: 6828167
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PROTEINS
CHEMICAL COMPOSITION
SYMPATHOLYTICS
BIOCHEMICAL REACTION KINETICS
BRAIN
FRACTIONATION
MOLECULAR WEIGHT
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CENTRAL NERVOUS SYSTEM
DRUGS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques