GABAB receptor-mediated inhibition of histamine H1-receptor-induced inositol phosphate formation in slices of rat cerebral cortex.
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.
Crawford
M L
ML
Department of Pharmacology, University of Cambridge, England.
Young
J M
JM
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007539:Isonicotinic Acids / Q000494:pharmacology; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology*; D013403:Sugar Phosphates / Q000096:biosynthesis*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D007295:Inositol Phosphates; D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D011969:Receptors, Histamine H1; D013403:Sugar Phosphates; D009118:Muscimol; D007294:Inositol; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D002217:Carbachol; D008094:Lithium; D001418:Baclofen; C015300:isoguvacine