1585261

Characterization of antagonistic activity and binding properties of SR 95531, a pyridazinyl-GABA derivative, in rat brain and cultured cerebellar neuronal cells.

Article date: 1992/4/1

PubMed ID: 1585261

Journal name: Synapse (New York, N.Y.) (ISSN: 0887-4476)

ABSTRACT

Experiments were performed to characterize the antagonistic activity and binding properties of SR 95531 [2-(3' carbethoxy-2'-propyl)-3-amino-6-paramethoxy-phenyl-piridazinium bromide] in rat brain. SR 95531 and bicuculline methiodide inhibited muscimol-stimulated 36Cl- uptake in cortical synaptoneurosomes in a concentration-dependent manner. The inhibitory potency of SR 95531 for the muscimol-stimulated 36Cl- uptake was 15 times higher than that of bicuculline methiodide. Scatchard plots of binding isotherms exhibited two apparent binding sites for [3H]SR 95531 in both the frontal cortex and cerebellum. The IC50 value of SR 95531 for muscimol-stimulated 36Cl- uptake into cortical synaptoneurosomes was in close agreement with the KD value of low-affinity binding sites of [3H]SR 95531 in the frontal cortex. Pretreatment of the membranes with phospholipase A2 invariably decreased [3H]SR 95531 binding in the frontal cortex and cerebellum. On the other hand, the treatment significantly increased [3H]gamma-aminobutyric acid (GABA) binding in a concentration-dependent manner in the frontal cortex. Although lower concentrations of phospholipase A2 did not affect [3H]GABA binding in the cerebellum, treatment with higher concentrations of phospholipase A2 increased the binding in this region. Specific binding of [3H]SR 95531 was also detected in cultures rich in cerebellar granule cells. Pretreatment with phospholipase A2 affected the binding of [3H]GABA and [3H]SR 95531 in these cells, as in the case of the cerebellum. These effects of phospholipase A2 on the binding of [3H]GABA and [3H]SR 95531 were partially prevented by the addition of delipidated bovine serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

This document is available from: http://directlinks.cc/files/muscimol/1585261.pdf

Author List: Ito Y, Koshiba T, Doi M, Asami S, Fukuda H, Murakoshi Y

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: GABA Antagonists; Pyridazines; Muscimol; Chlorine; gabazine;

Mesh terms: Animals; Brain/drug effects; Cells, Cultured; Cerebellum/drug effects; Cerebral Cortex/drug effects; Chlorine/metabolism; GABA Antagonists; Kinetics; Male; Muscimol/antagonists & inhibitors; Neurons/drug effects; Pyridazines/metabolism; Rats; Rats, Inbred Strains; Synaptosomes/drug effects;

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