Neurochemical studies on GABA receptor (VIII). Enhancement of 3H-muscimol binding to synaptic membrane by unsaturated free fatty acids.

Abstract

Pretreatment of cerebral synaptic membrane with phospholipase (PLase)A2 as well as PLase C resulted in a significant facilitation of 3H-muscimol binding. In addition, it was found that a significant facilitation of 3H-muscimol binding was induced by pretreating synaptic membrane with unsaturated free fatty acids such as arachidonic acid(ARA) and linoleic acid. The stimulatory action of ARA on the binding was significantly enhanced by the addition of lipoxygenase, whereas in vitro addition of various prostaglandins(E1, E2, F2 α, D2 and I2), cyclo-oxygenase products, had no profound effects on the binding. No significant correlation was observed between lipid peroxides formation in the membrane and the enhancement of 3H-muscimol binding induced by PLase A2, PLase C and ARA. On the other hand, 3H-muscimol binding was significantly elevated by the pretreatment of membrane with xanthine and xanthine oxidase, a superoxide anion generating system. The enhancement of 3H-muscimol binding by PLase A2 was also suppressed significantly by the addition of various scavengers for superoxide anion such as superoxide dis-mutase, tiron and nitroblue tetrazolium. These results suggest that PLase A2 may stimulate GABA receptor binding through the production of active oxygens including superoxide anion which can be originated from unsaturated free fatty acids released from membrane phospholipids by the action of this enzyme.