Yamakura T, Harris R A
Waggoner Center for Alcohol and Addiction Research and Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA.
Anesthesiology. 2000 Oct;93(4):1095-101. doi: 10.1097/00000542-200010000-00034.
Ligand-gated ion channels are considered to be potential general anesthetic targets. Although most general anesthetics potentiate the function of gamma-aminobutyric acid receptor type A (GABAA), the gaseous anesthetics nitrous oxide and xenon are reported to have little effect on GABAA receptors but inhibit N-methyl-d-aspartate (NMDA) receptors. To define the spectrum of effects of nitrous oxide and xenon on receptors thought to be important in anesthesia, the authors tested these anesthetics on a variety of recombinant brain receptors.
The glycine, GABAA, GABA receptor type C (GABAC), NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate, 5-hydroxytryptamine3 (5-HT3), and nicotinic acetylcholine (nACh) receptors were expressed in Xenopus oocytes and effects of nitrous oxide and xenon, and as equipotent concentrations of isoflurane and ethanol, were studied using the two-electrode voltage clamp.
Nitrous oxide (0.58 atmosphere [atm]) and xenon (0.46 atm) exhibited similar effects on various receptors. Glycine and GABAA receptors were potentiated by gaseous anesthetics much less than by isoflurane, whereas nitrous oxide inhibited GABAC receptors. Glutamate receptors were inhibited by gaseous anesthetics more markedly than by isoflurane, but less than by ethanol. NMDA receptors were the most sensitive among glutamate receptors and were inhibited by nitrous oxide by 31%. 5-HT3 receptors were slightly inhibited by nitrous oxide. The nACh receptors were inhibited by gaseous and volatile anesthetics, but ethanol potentiated them. The sensitivity was different between alpha4beta2 and alpha4beta4 nACh receptors; alpha4beta2 receptors were inhibited by nitrous oxide by 39%, whereas alpha4beta4 receptors were inhibited by 7%. The inhibition of NMDA and nACh receptors by nitrous oxide was noncompetitive and was slightly different depending on membrane potentials for NMDA receptors, but not for nACh receptors.
Nitrous oxide and xenon displayed a similar spectrum of receptor actions, but this spectrum is distinct from that of isoflurane or ethanol. These results suggest that NMDA receptors and nACh receptors composed of beta2 subunits are likely targets for nitrous oxide and xenon.
配体门控离子通道被认为是潜在的全身麻醉靶点。尽管大多数全身麻醉药可增强γ-氨基丁酸A型（GABAA）受体的功能，但据报道，气态麻醉药氧化亚氮和氙对GABAA受体几乎没有影响，却能抑制N-甲基-D-天冬氨酸（NMDA）受体。为了确定氧化亚氮和氙对麻醉中重要受体的作用谱，作者对多种重组脑受体进行了这些麻醉药的测试。
将甘氨酸、GABAA、GABA C型受体（GABAC）、NMDA、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）、海人藻酸、5-羟色胺3（5-HT3）和烟碱型乙酰胆碱（nACh）受体在非洲爪蟾卵母细胞中表达，并使用双电极电压钳研究氧化亚氮和氙以及等效浓度的异氟烷和乙醇的作用。
氧化亚氮（0.58个大气压[atm]）和氙（0.46 atm）对各种受体表现出相似的作用。气态麻醉药对甘氨酸和GABAA受体的增强作用远小于异氟烷，而氧化亚氮抑制GABAC受体。气态麻醉药对谷氨酸受体的抑制作用比异氟烷更明显，但比乙醇小。NMDA受体是谷氨酸受体中最敏感的，被氧化亚氮抑制31%。5-HT3受体被氧化亚氮轻微抑制。nACh受体被气态和挥发性麻醉药抑制，但乙醇使其增强。α4β2和α4β4 nACh受体的敏感性不同；α4β2受体被氧化亚氮抑制39%，而α4β4受体被抑制7%。氧化亚氮对NMDA和nACh受体的抑制是非竞争性的，并且根据NMDA受体的膜电位略有不同，但对nACh受体则不然。
氧化亚氮和氙表现出相似的受体作用谱，但该谱与异氟烷或乙醇的不同。这些结果表明，由β2亚基组成的NMDA受体和nACh受体可能是氧化亚氮和氙的靶点。
