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• W4245802474 abstract "A naturally occurring brain lipid, cis-9,10-octadeceamideoleamide (OA), is found in increased concentrations in the cerebrospinal fluid of sleep-deprived cats, which suggests that it may be an endogenous sleep-inducing substance. We studied the effects of this fatty-acid derivative on the function of cloned gamma-aminobutyric acid (GABAA) receptors expressed in Xenopus oocytes. Oocytes were injected with cRNA synthesized in vitro to express simple GABAA receptors (alpha 1 beta 1, alpha 3 beta 1, alpha 5 beta 1, and alpha 1 beta 2 subunit combinations) and receptors in which the GABA-induced chloride currents were potentiated in the presence of benzodiazepines (alpha 1 beta 1 gamma 2s and alpha 1 beta 2 gamma 2s subunit combinations). OA only produced significant potentiation of the peak Cl- current when applied with GABA to benzodiazepine-sensitive GABAA receptors. The peak currents of the simple GABAA receptors in the presence of OA were either unaffected or slightly inhibited by OA, but the overall mean currents were not significantly altered. Oleic acid was also capable of potentiating benzodiazepine-sensitive GABAA receptor function. The function of other ligand-gated ion channels, such as the N-methyl-D-aspartate receptor (NR1 + NR2A or 2C) and the 5-HT3 receptor expressed in Xenopus oocytes, were unaffected by OA. Sprague-Dawley rats receiving intraperitoneal injections of oleamide (10, 20, or 100 mg/kg) showed no change in the minimum alveolar anesthetic concentration (MAC) of desflurane required to abolish movement in response to noxious (tail clamp) stimulation (control MAC 6.48% +/- 1.28% atm; 100 mg/kg OA MAC 7.05% +/- 0.42% atm). These results reinforce the view that oleyl compounds may be natural modulators of inhibitory ion channel function, but that these effects contribute little to the central nervous system depression produced by volatile anesthetics as measured by MAC. Implications: The putative sleep-inducing substance, oleamide, potentiates benzodiazepinesensitive gamma-aminobutyric acid receptor function but does not alter desflurane minimum alveolar anesthetic concentration in rats. (Anesth Analg 1998;86:1294-300)" @default.
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• W4245802474 date "1998-06-01" @default.
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• W4245802474 title "Oleamide Potentiates Benzodiazepine-Sensitive gamma-Aminobutyric Acid Receptor Activity but Does Not Alter Minimum Alveolar Anesthetic Concentration" @default.
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• W4245802474 doi "https://doi.org/10.1213/00000539-199806000-00031" @default.
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