2831297

Heterogeneity of gamma-aminobutyric acid/benzodiazepine/beta-carboline receptor complex in rat spinal cord.

Article date: 1988/4/1

PubMed ID: 2831297

Journal name: Journal of neurochemistry (ISSN: 0022-3042)

ABSTRACT

The properties of muscimol, beta-carboline (BC), and benzodiazepine (BZD) binding to crude synaptic membranes were studied in the spinal cord and cerebellum of rats. In cerebellar membranes, the density of high-affinity [3H]muscimol and [3H]6,7-dimethoxy-4-ethyl-beta-carboline ([3H]BCCM) binding sites is almost identical to that of [3H]flunitrazepam ([3H]FLU) or [3H]flumazenil (Ro 15-1788; ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1-4]benzodiazepine-3-carboxylate). In contrast to the cerebellum, the number of muscimol and BC binding sites in rat spinal cord is approximately 20-25% of the number of FLU or flumazenil binding sites. Moreover, in spinal cord membranes, BC recognition site ligands displace [3H]-flumazenil bound to those sites, with low affinity and a Hill slope significantly less than 1; the potency of the different BCs in displacing [3H]flumazenil is 20-50-fold lower in the spinal cord than in the cerebellum. [3H]Flumazenil is not displaced from spinal cord membranes by the peripheral BZD ligand Ro 5-4864 (4'-chlorodiazepam), whereas it is displaced with low affinity and a Hill slope of less than 1 (nH = 0.4) by CL 218,872 (3-methyl-6-(3-trifluoromethylphenyl)-1,2,4-triazolol[4,3-b] pyridazine). These data suggest that a large number of BZD binding sites in spinal cord (approximately 80%) are of the central-type, BZD2 subclass, whereas the BZD binding sites in cerebellum are predominantly of the central-type, BZD1 subclass.(ABSTRACT TRUNCATED AT 250 WORDS)

This document is available from: http://directlinks.cc/files/muscimol/2831297.pdf

Author List: Santi M R, Cox D H, Guidotti A

Publication Types: Comparative Study; Journal Article

Substances mentioned in the article: Carbolines; Receptors, GABA-A; methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; Muscimol; Flumazenil; gamma-Aminobutyric Acid; Flunitrazepam; Diazepam; Bicuculline;

Mesh terms: Animals; Bicuculline/pharmacology; Binding, Competitive; Carbolines/metabolism; Cerebellum/metabolism; Diazepam/metabolism; Flumazenil/metabolism; Flunitrazepam/metabolism; Male; Muscimol/metabolism; Rats; Receptors, GABA-A/metabolism; Spinal Cord/metabolism; Synaptic Membranes/metabolism; gamma-Aminobutyric Acid/pharmacology;

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