Temperature dependence and GABA modulation of (TH)triazolam binding in the rat brain

Journal Article · Mon Jul 27 00:00:00 EDT 1987 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(87)90214-1· OSTI ID:6417056

Earle, M E; Concas, A; Wamsley, J K; Yamamura, H I

The hypnotic triazolam (TZ), a triazolobenzodiazepine displays a short physiological half life and has been used for the treatment of insomnia related to anxiety states. The authors major objectives were the direct measurement of the temperature dependence and the gamma-aminobutyric acid (GABA) effect of (TH)TZ binding in the rat brain. Saturation studies showed a shift to lower affinity with increasing temperatures (K/sub d/ = 0.27 +/- 08 nM at 0C; K/sub d/ = 1.96 +/- 0.85 nM at 37C) while the B/sub max/ values remained unchanged (1220 +/- 176 fmoles/mg protein at 0C and 1160 +/- 383 fmoles/mg protein at 37C). Saturation studies of (TH)TZ binding in the presence or absence of GABA (100 M) showed a GABA-shift. At 0C the K/sub d/ values were (K/sub d/ = 0.24 +/- 0.03 nM/-GABA; K/sub d/ = 0.16 +/- 0.04/+GABA) and at 37C the K/sub d/ values were (K/sub d/ = 1.84 +/- 0.44 nM/-GABA; K/sub d/ = 0.95 +/- 0.29 nM/+GABA). In contrast to reported literature, the authors findings show that TZ interacts with benzodiazepine receptors with a temperature dependence and GABA-shift consistent with predicted behavior for benzodiazepine agonists. 20 references, 3 tables.

• Research Organization: Univ. of Arizona, Tucson
• OSTI ID: 6417056
• Journal Information: Life Sci.; (United States), Vol. 41:4
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HYPNOTICS AND SEDATIVES
BIOCHEMICAL REACTION KINETICS
METHADONE HYDROCHLORIDE
RECEPTORS
AFFINITY
BRAIN
EXPERIMENTAL DATA
RATS
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
BODY
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DATA
DRUGS
INFORMATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
NARCOTICS
NERVOUS SYSTEM
NUMERICAL DATA
ORGANS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques