Ori C, Ford-Rice F, London E D
National Institute on Drug Abuse (NIDA) Addiction Research Center, Baltimore, Maryland 21224.
Anesthesiology. 1989 Mar;70(3):541-4. doi: 10.1097/00000542-198903000-00027.
The effects of two general anesthetics, nitrous oxide and halothane, and oxygen on mu and kappa opioid receptor subtypes from guinea-pig brain were investigated. mu receptor binding was defined using [3H]dihydromorphine as the ligand. Nitrous oxide (100%) and halothane (2%) decreased the [3H]dihydromorphine binding affinity (Kdair = 0.87 nM, KdN2O = 1.45 nM, Kdhalothane = 2.30 nM) without affecting the density of binding sites. A decrease in the [3H]dihydromorphine binding affinity without influence on the density of binding sites was also observed in the presence of 100% oxygen (KdO2 = 1.40 nM). kappa receptor binding was defined using 3Hethylketocyclazocine as the ligand, in the presence of 100 nM D-ala2-D-leu5-enkephalin and 30 nM morphine. While 100% nitrous oxide caused a slight decrease in 3Hethylketocyclazocine binding affinity (Kdair = 0.24 nM, KdN2O = 0.31 nM) and a substantial decrease in the density of binding sites (Bmaxair = 115 fmol/mg protein, BmaxN2O = 84 fmol/mg protein), halothane dramatically affected both the affinity (Kdhalothane = 0.70 nM) and density (Bmaxhalothane = 38 fmol/mg protein). Oxygen (100%) reduced [3H]dihydromorphine binding affinity. Differential effects of two anesthetics on the same receptor or distinct actions of the same anesthetic on different receptors could indicate the presence of specific targets for anesthetics at the membrane level. Conversely, effects of volatile anesthetics on opioid receptors could reflect a non-specific perturbation of the lipidic and proteinaceous components of the membranes.
研究了两种全身麻醉剂氧化亚氮和氟烷以及氧气对豚鼠脑内μ和κ阿片受体亚型的影响。使用[³H]二氢吗啡作为配体来定义μ受体结合。氧化亚氮（100%）和氟烷（2%）降低了[³H]二氢吗啡的结合亲和力（Kd空气 = 0.87 nM，Kd氧化亚氮 = 1.45 nM，Kd氟烷 = 2.30 nM），但不影响结合位点的密度。在100%氧气存在的情况下，也观察到[³H]二氢吗啡结合亲和力降低而结合位点密度不受影响（Kd氧气 = 1.40 nM）。使用³H乙基酮环唑新作为配体，在100 nM D - ala2 - D - leu5 - 脑啡肽和30 nM吗啡存在的情况下定义κ受体结合。虽然100%氧化亚氮导致³H乙基酮环唑新结合亲和力略有降低（Kd空气 = 0.24 nM，Kd氧化亚氮 = 0.31 nM）且结合位点密度大幅降低（Bmax空气 = 115 fmol/mg蛋白质，Bmax氧化亚氮 = 84 fmol/mg蛋白质），但氟烷对亲和力（Kd氟烷 = 0.70 nM）和密度（Bmax氟烷 = 38 fmol/mg蛋白质）都有显著影响。氧气（100%）降低了[³H]二氢吗啡的结合亲和力。两种麻醉剂对同一受体的不同作用或同一麻醉剂对不同受体的不同作用可能表明麻醉剂在膜水平存在特定靶点。相反，挥发性麻醉剂对阿片受体的作用可能反映了膜的脂质和蛋白质成分的非特异性扰动。
