Oleamide potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor activity but does not alter minimum alveolar anesthetic concentration.

摘要: UNLABELLED A naturally occurring brain lipid, cis-9,10-octadeceamide--oleamide (OA), is found in increased concentrations the cerebrospinal fluid of sleep-deprived cats, which suggests that it may be an endogenous sleep-inducing substance. We studied effects this fatty-acid derivative on function cloned gamma-aminobutyric acid (GABA(A)) receptors expressed Xenopus oocytes. Oocytes were injected with cRNA synthesized vitro to express simple GABA(A) (alpha1beta1, alpha3beta1, alpha5beta1, and alpha1beta2 subunit combinations) GABA-induced chloride currents potentiated presence benzodiazepines (alpha1beta1gamma2s alpha1beta2gamma2s combinations). OA only produced significant potentiation peak Cl- current when applied GABA benzodiazepine-sensitive receptors. The either unaffected or slightly inhibited by OA, but overall mean not significantly altered. Oleic was also capable potentiating receptor function. other ligand-gated ion channels, such as N-methyl-D-aspartate (NR1 + NR2A 2C) 5-HT3 oocytes, OA. Sprague-Dawley rats receiving intraperitoneal injections oleamide (10, 20, 100 mg/kg) showed no change minimum alveolar anesthetic concentration (MAC) desflurane required abolish movement response noxious (tail clamp) stimulation (control MAC 6.48% +/- 1.28% atm; mg/kg 7.05% 0.42% atm). These results reinforce view oleyl compounds natural modulators inhibitory channel function, these contribute little central nervous system depression volatile anesthetics measured MAC. IMPLICATIONS putative substance, oleamide, potentiates does alter rats.