Fiorica-Howells E, Gambale F, Horn R, Osses L, Spector S
Neurosciences Department, Roche Institute of Molecular Biology, Nutley, New Jersey.
J Pharmacol Exp Ther. 1990 Feb;252(2):610-5.
We investigated the effect of phencyclidine (PCP) on the voltage-dependent K+ current in whole cell recordings from murine thymocytes. PCP caused a dramatic, reversible and dose-dependent decrease of the current. An analysis of the dose-response relationship suggests a single site of action for PCP with an IC50 of 4.7 microM. Dextrorphan and naloxone also inhibited the current, although their effects were of a lower magnitude than those of PCP. Neither 10 microM dextrorphan nor 100 microM naloxone antagonized the inhibitory action of 10 microM PCP. The analysis of the dose-response curve for PCP in presence of 100 microM naloxone suggested that the two drugs act at the same site. We also investigated the effect of morphine on the K+ current. Morphine, in concentrations up to 100 microM, inhibited the K+ current less than dextrorphan or PCP. The kinetics and voltage dependence of the currents in the presence of morphine suggest that it interacts with a different site or different conformation of the channel than the other three compounds. Our findings show that certain opioids can act on thymocytes through a system completely different from the typical opioid receptors.
我们研究了苯环己哌啶（PCP）对从小鼠胸腺细胞进行全细胞记录时电压依赖性钾电流的影响。PCP导致电流急剧、可逆且剂量依赖性地降低。剂量 - 反应关系分析表明PCP有一个单一作用位点，其半数抑制浓度（IC50）为4.7微摩尔。右啡烷和纳洛酮也抑制该电流，尽管它们的作用程度低于PCP。10微摩尔右啡烷和100微摩尔纳洛酮均未拮抗10微摩尔PCP的抑制作用。在存在100微摩尔纳洛酮的情况下对PCP剂量 - 反应曲线的分析表明这两种药物作用于同一位点。我们还研究了吗啡对钾电流的影响。浓度高达100微摩尔的吗啡对钾电流的抑制作用小于右啡烷或PCP。存在吗啡时电流的动力学和电压依赖性表明，它与其他三种化合物作用于通道的不同位点或不同构象。我们的研究结果表明，某些阿片类药物可通过一个与典型阿片受体完全不同的系统作用于胸腺细胞。
