Potentiation and inhibition of ionotropic neurotransmitter receptors expressed in Xenopus oocyte by linoleic acid and its hydroperoxide.
To study the effects of lipid hydroperoxide on ionotropic neurotransmitter receptors, gamma-aminobutyric acid (GABA), N-methyl-D-aspartate (NMDA), and non-NMDA receptors (GABARs, NMDARs, and non-NMDARs, respectively) were expressed in Xenopus oocytes that received an injection of mRNA prepared from rat whole brain. Linoleic acid (LA) and its hydroperoxide 13-L-hydroperoxylinoleic acid (LOOH) prepared with soybean lipoxygenase inhibited the response of GABARs in the presence of GABA at high concentrations. The inhibition was stronger when the inhibitors were perfused 1 min before a mixture of GABA and the inhibitors than when they were perfused simultaneously with GABA. On the other hand, only LOOH potentiated the response of GABARs in the presence of GABA at low concentrations, possibly increasing the affinity of GABA to the receptors. Both LA and LOOH accelerated the rate of desensitization of GABARs, but LOOH did not affect their equilibrium between the active and desensitized form of the receptors. They also inhibited the response of NMDARs in a noncompetitive manner but barely inhibited the response of non-NMDARs in the presence of kainate at various concentrations. These results suggest the possibility that production of lipid hydroperoxide modulates the neural transmission in the brain, especially through GABARs.
Aoshima
H
H
Department of Chemistry, Faculty of Liberal Arts, Yamaguchi University, Japan.
D000818:Animals; D004357:Drug Synergism; D004594:Electrophysiology; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D014981:Xenopus / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D008041:Linoleic Acids; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D019787:Linoleic Acid; C032890:13-hydroperoxylinoleic acid; D007608:Kainic Acid