Yost C S, Hampson A J, Leonoudakis D, Koblin D D, Bornheim L M, Gray A T
Department of Anesthesia, University of California-San Francisco 94143-0542, USA.
Anesth Analg. 1998 Jun;86(6):1294-300. doi: 10.1097/00000539-199806000-00031.
A naturally occurring brain lipid, cis-9,10-octadeceamide--oleamide (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 (GABA(A)) receptors expressed in Xenopus oocytes. Oocytes were injected with cRNA synthesized in vitro to express simple GABA(A) receptors (alpha1beta1, alpha3beta1, alpha5beta1, and alpha1beta2 subunit combinations) and receptors in which the GABA-induced chloride currents were potentiated in the presence of benzodiazepines (alpha1beta1gamma2s and alpha1beta2gamma2s subunit combinations). OA only produced significant potentiation of the peak Cl- current when applied with GABA to benzodiazepine-sensitive GABA(A) receptors. The peak currents of the simple GABA(A) 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 GABA(A) 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.
The putative sleep-inducing substance, oleamide, potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor function but does not alter desflurane minimum alveolar anesthetic concentration in rats.
一种天然存在的脑脂质，顺式-9,10-十八碳酰胺——油酰胺（OA），在睡眠剥夺的猫的脑脊液中浓度升高，这表明它可能是一种内源性促眠物质。我们研究了这种脂肪酸衍生物对非洲爪蟾卵母细胞中表达的克隆γ-氨基丁酸（GABA(A)）受体功能的影响。向卵母细胞注射体外合成的cRNA以表达简单的GABA(A)受体（α1β1、α3β1、α5β1和α1β2亚基组合）以及在存在苯二氮䓬类药物时GABA诱导的氯离子电流增强的受体（α1β1γ2s和α1β2γ2s亚基组合）。仅当OA与GABA一起应用于对苯二氮䓬敏感的GABA(A)受体时，OA才会显著增强氯离子电流峰值。在OA存在下，简单GABA(A)受体的峰值电流要么未受影响，要么被OA轻微抑制，但总体平均电流没有显著改变。油酸也能够增强对苯二氮䓬敏感的GABA(A)受体功能。其他配体门控离子通道的功能，如非洲爪蟾卵母细胞中表达的N-甲基-D-天冬氨酸受体（NR1 + NR2A或2C）和5-HT3受体，不受OA影响。接受腹腔注射油酰胺（10、20或100 mg/kg）的Sprague-Dawley大鼠，在对有害（夹尾）刺激产生运动反应时，所需的地氟烷最低肺泡麻醉浓度（MAC）没有变化（对照MAC 6.48%±1.28% atm；100 mg/kg OA MAC 7.05%±0.42% atm）。这些结果强化了这样一种观点，即油酰化合物可能是抑制性离子通道功能的天然调节剂，但这些作用对挥发性麻醉剂通过MAC测量产生的中枢神经系统抑制作用贡献不大。
假定的促眠物质油酰胺增强对苯二氮䓬敏感的γ-氨基丁酸受体功能，但不改变大鼠地氟烷的最低肺泡麻醉浓度。
