2447244

Regulation of gamma-aminobutyric acid/barbiturate receptor-gated chloride ion flux in brain vesicles by phospholipase A2: possible role of oxygen radicals.

Article date: 1988/2/1

PubMed ID: 2447244

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

ABSTRACT

Preincubation of brain membranes with phospholipase A2 (PLA2) has been shown previously to affect the binding characteristics of various recognition sites associated with the gamma-aminobutyric acid (GABA) receptor complex. In the present study, we have investigated the effects of PLA2 (from Naja naja siamensis venom) on the functional activity of the GABA receptor/chloride ion channel. PLA2 (0.001-0.02 U/mg protein) preincubation decreased pentobarbital-induced 36Cl- efflux and muscimol-induced 36Cl- uptake in rat cerebral cortical synaptoneurosomes. The effect of PLA2 was prevented by EGTA and two nonselective PLA2 inhibitors, mepacrine and bromophenacyl bromide. The removal of free fatty acids by addition of bovine serum albumin both prevented and reversed the effect of PLA2. Products of the catalytic activity of PLA2, such as the unsaturated free fatty acids, arachidonic and oleic acids, mimicked the effect of PLA2. However, the saturated fatty acid, palmitic acid, and lysophosphatidyl choline had no effect on pentobarbital-induced 36Cl- efflux. Because unsaturated free fatty acids are highly susceptible to peroxidation by oxygen radicals, the role of oxygen radicals was investigated. Xanthine plus xanthine oxidase, a superoxide radical generating system, mimicked the effect of PLA2, whereas the superoxide radical scavenger, superoxide dismutase, diminished the effects of PLA2 and arachidonic acid on pentobarbital-induced 36Cl- efflux. Similarly, the effect of PLA2 was also inhibited by methanol (1 mM), a scavenger of the hydroxyl radical, and by catalase. These data indicate that exogenously added PLA2 induces alterations in membrane phospholipids, possibly promoting the generation of oxygen radicals and fatty acid peroxides which can ultimately modulate GABA/barbiturate receptor function in brain.

This document is available from: http://directlinks.cc/files/muscimol/2447244.pdf

Author List: Schwartz R D, Skolnick P, Paul S M

Publication Types: Journal Article

Substances mentioned in the article: Acetophenones; Chlorides; Fatty Acids; Free Radicals; Ion Channels; Receptors, GABA-A; Receptors, Neurotransmitter; Xanthines; barbiturate receptor; Xanthine; Serum Albumin, Bovine; Superoxide Dismutase; Xanthine Oxidase; Phospholipases; Phospholipases A; Phospholipases A2; Quinacrine; Pentobarbital; 4-bromophenacyl bromide; Oxygen;

Mesh terms: Acetophenones/pharmacology; Animals; Brain/metabolism; Chlorides/metabolism; Fatty Acids/metabolism; Free Radicals; Ion Channels/physiology; Male; Oxygen/metabolism; Pentobarbital/pharmacology; Phospholipases/metabolism; Phospholipases A/antagonists & inhibitors; Phospholipases A2; Quinacrine/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/physiology; Receptors, Neurotransmitter/physiology; Serum Albumin, Bovine/pharmacology; Superoxide Dismutase/pharmacology; Synaptosomes/metabolism; Xanthine; Xanthine Oxidase/pharmacology; Xanthines/pharmacology;

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