Premium
GABA B Receptor‐Mediated Inhibition of Histamine H 1 ‐Receptor‐Induced Inositol Phosphate Formation in Slices of Rat Cerebral Cortex
Author(s) -
Crawford Melissa L. A.,
Young J. Michael
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb01109.x
Subject(s) - histamine , inositol phosphate , baclofen , agonist , inositol , chemistry , gabab receptor , medicine , endocrinology , receptor , biology , biochemistry
Histamine‐stimulated accumulation of [ 3 H]inositol monophosphate ([ 3 H]IP,) in lithium‐treated slices of rat cerebral cortex was inhibited by γ‐aminobutyric acid (GABA) (IC 50 0.30 ± 0.03 m M ). The maximum level of inhibition was 69 ± 2%. GABA alone caused a small stimulation of basal accumulation of [ 3 H]IP 1 . The inhibitory action of GABA on the response to histamine was mimicked by the GABAb agonist (‐)‐baclofen, IC 50 0.69 ± 0.04 μ M , which was 430‐fold more potent as an inhibitor than the (+)‐isomer. (‐)‐Baclofen also inhibited histamine‐induced formation of [ 3 H]inositol bisphosphate ([ 3 H]IP 2 ) and [ 3 H]inositol trisphosphate ([ 3 H]IP 3 ). Inhibition curves for GABA and for (‐)‐and (+)‐baclofen had Hill coefficients greater than unity. (—)‐ Baclofen, at concentrations that caused inhibition of histamine‐induced [ 3 H]IP 1 accumulation, did not alter the basal level of [ 3 H]IP 1 or the incorporation of [ 3 H]inositol into total inositol phospholipids. Isoguvacine, a GABA A agonist, had no effect on either the histamine‐stimulated or basal accumulation of [ 3 H]IP 1 . GABA had no effect on carbachol‐stimulated [ 3 H]IP 1 formation.