Phospholipase C activation induced by noradrenaline in rat hippocampal slices is potentiated by GABA-receptor stimulation.

Abstract

We have studied the effect of -y-aminobutyric acid (GABA) and other GABA-receptor agonists (3-aminopropanesulphonic acid and muscimol) on the noradrenaline-induced stimulation of polyphosphoinositide metabolism in rat hippocampal slices. Formation of water-soluble inositol phosphates, and polyphosphoinositide metabolism were studied in hippocampal slices prelabelied with [3H]myoinositol. Noradrenaline induced formation of inositol mono-, bisand trisphosphate during 10 min incubation in the presence of lithium; activation of phospholipase C by noradrenaline was also reflected by the hydrolysis of polyphosphoinositides and by the increased metabolism of phosphatidylinositol. GABAreceptor agonists were unable to activate per se phospholipase C; however, when added together with a low concentration of noradrenaline, they greatly potentiated the noradrenaline-stimulated polyphosphoinositide metabolism. We conclude that GABA-receptor agonists potentiate the effect of noradrenaline on polyphosphoinositide turnover and we discuss the role of this neurotransmitter interaction in the physiology of the hippocampus.

GABAB Receptor‐Mediated Inhibition of Histamine H1‐Receptor‐Induced Inositol Phosphate Formation in Slices of Rat Cerebral Cortex

“…This implies that GABA has more than one action on phosphoinositide metabolism in rat cerebral cortex. The effect on basal level is not obviously related to the recently described stirnulatory action of GABA on noradrenaline-induced inositol phosphate formation in rat hippocampus, which appears to be GABAA receptor mediated Ruggiero et al, 1987). Isoguvacine had no significant effect on either histamine-stimulated or basal [3H]IP1 levels in our experiments.…”

Potentiation by γ‐Aminobutyric Acid of α1‐Agonist‐Induced Accumulation of Inositol Phosphates in Slices of Rat Cerebral Cortex

“…y-Aminobutyric acid (GABA), acting on GABAB receptors, inhibits histamine-induced formation of 3Hinositol phosphates (3H-IPs) in lithium-treated slices of rat cerebral cortex preincubated with [3H]inositol (Crawford and Young,1 9 8 8~) but has no effect on the response to carbachol in the same tissue (Brown et al, 1984; Crawford and Young, 1988~). In contrast, in slices of rat hippocampus, GABA has been reported to enhance noradrenaline-induced polyphosphoinositide metabolism by an action at GABAA receptors Ruggiero et al, 1987). If GABA had the same effect in rat cerebral cortex, then the outcome of combination with GABA on agonist-induced phosphoinositide metabolism would be different for histamine, carbachol, and noradrenaline.…”

Ammonium acetate inhibits ionotropic receptors and differentially affects metabotropic receptors for glutamate

“…The upper phase (2 ml) which contained the water-soluble [3HI inositol phosphates (inositol monophosphate, IP; inositol 1,4-bisphosphate, IP2; inositol 1,4,5-trisphosphate, IP3) was transferred to test-tubes and water (3 ml) was added. The inositol phosphates were then separated on Dowex AG 1-X 8 anion exchange resin (formiate form, 100-200 mesh) as previously described (Ruggiero et al, 1987). The radioactivity in portions (8 ml) of these fractions was determined by liquid scintillation counting.…”