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

Publication ,  Journal Article
Schwartz, RD; Skolnick, P; Paul, SM
Published in: J Neurochem
February 1988

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.

Duke Scholars

Published In

J Neurochem

DOI

ISSN

0022-3042

Publication Date

February 1988

Volume

50

Issue

2

Start / End Page

565 / 571

Location

England

Related Subject Headings

  • Xanthines
  • Xanthine Oxidase
  • Xanthine
  • Synaptosomes
  • Superoxide Dismutase
  • Serum Albumin, Bovine
  • Receptors, Neurotransmitter
  • Receptors, GABA-A
  • Rats, Inbred Strains
  • Rats
 

Citation

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Schwartz, R. D., Skolnick, P., & Paul, S. M. (1988). Regulation of gamma-aminobutyric acid/barbiturate receptor-gated chloride ion flux in brain vesicles by phospholipase A2: possible role of oxygen radicals. J Neurochem, 50(2), 565–571. https://doi.org/10.1111/j.1471-4159.1988.tb02948.x
Schwartz, R. D., P. Skolnick, and S. M. Paul. “Regulation of gamma-aminobutyric acid/barbiturate receptor-gated chloride ion flux in brain vesicles by phospholipase A2: possible role of oxygen radicals.J Neurochem 50, no. 2 (February 1988): 565–71. https://doi.org/10.1111/j.1471-4159.1988.tb02948.x.
Schwartz, R. D., et al. “Regulation of gamma-aminobutyric acid/barbiturate receptor-gated chloride ion flux in brain vesicles by phospholipase A2: possible role of oxygen radicals.J Neurochem, vol. 50, no. 2, Feb. 1988, pp. 565–71. Pubmed, doi:10.1111/j.1471-4159.1988.tb02948.x.
Journal cover image

Published In

J Neurochem

DOI

ISSN

0022-3042

Publication Date

February 1988

Volume

50

Issue

2

Start / End Page

565 / 571

Location

England

Related Subject Headings

  • Xanthines
  • Xanthine Oxidase
  • Xanthine
  • Synaptosomes
  • Superoxide Dismutase
  • Serum Albumin, Bovine
  • Receptors, Neurotransmitter
  • Receptors, GABA-A
  • Rats, Inbred Strains
  • Rats