GABAB receptor-mediated inhibition of histamine H1-receptor-induced inositol phosphate formation in slices of rat cerebral cortex.

Article date: 1988/11/1

PubMed ID: 2844993

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


Histamine-stimulated accumulation of [3H]inositol monophosphate ([3H]IP1) in lithium-treated slices of rat cerebral cortex was inhibited by gamma-aminobutyric acid (GABA) (IC50 0.30 +/- 0.03 mM). The maximum level of inhibition was 69 +/- 2%. GABA alone caused a small stimulation of basal accumulation of [3H]IP1. The inhibitory action of GABA on the response to histamine was mimicked by the GABAB agonist (-)-baclofen, IC50 0.69 +/- 0.04 microM, which was 430-fold more potent as an inhibitor than the (+)-isomer. (-)-Baclofen also inhibited histamine-induced formation of [3H]inositol bisphosphate ([3H]IP2) and [3H] inositol trisphosphate ([3H]IP3). Inhibition curves for GABA and for (-)-and and (+)-baclofen had Hill coefficients greater than unity. (-)-Baclofen, at concentrations that caused inhibition of histamine-induced [3H]IP1 accumulation, did not alter the basal level of [3H]IP1 or the incorporation of [3H]inositol into total inositol phospholipids. Isoguvacine, a GABAA agonist, had no effect on either the histamine-stimulated or basal accumulation of [3H]IP1. GABA had no effect on carbachol-stimulated [3H]IP1 formation.

This document is available from: http://directlinks.cc/files/muscimol/2844993.pdf

Author List: Crawford M L, Young J M

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

Substances mentioned in the article: Inositol Phosphates; Isonicotinic Acids; Receptors, GABA-A; Receptors, Histamine H1; Sugar Phosphates; Muscimol; Inositol; gamma-Aminobutyric Acid; Histamine; Carbachol; Lithium; Baclofen; isoguvacine;

Mesh terms: Animals; Baclofen/pharmacology; Carbachol/pharmacology; Cerebral Cortex/drug effects; Histamine/pharmacology; Inositol/metabolism; Inositol Phosphates/biosynthesis; Isonicotinic Acids/pharmacology; Kinetics; Lithium/pharmacology; Male; Muscimol/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/physiology; Receptors, Histamine H1/physiology; Sugar Phosphates/biosynthesis; gamma-Aminobutyric Acid/pharmacology;

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