Jones S M, Snell L D, Johnson K M
J Pharmacol Exp Ther. 1987 Feb;240(2):492-7.
We have reported previously that phencyclidine (PCP) antagonizes N-methyl-D-aspartate (NMDA)-induced release of dopamine and acetylcholine from slices of rat striatum and nucleus accumbens. In the present experiments, we examined the effect of PCP on NMDA and kainic acid (KA)-induced release of [3H]norepinephrine (NE) from superfused rat hippocampal slices. NMDA and KA stimulated the efflux of NE with EC50 values of 192 and 245 microM, respectively. The presence of 1.2 mM MgCl2 in the buffer abolished NMDA-induced release but had little effect on KA-induced release. PCP inhibited the release of [3H]NE induced by 100 microM NMDA with an IC50 of 46 nM, but had no effect on the release of NE stimulated by 300 microM KA. 2-Aminophosphonovalerate antagonized NMDA-induced release, producing a parallel shift to the right in the concentration-response curve. However, PCP shifted the concentration-response curve to the right in a nonparallel fashion. Drugs with PCP-like properties, such as dexoxadrol and cyclazocine, inhibited NMDA-induced release, whereas related drugs such as levoxadrol, ethylketocyclazocine and morphine, which are not PCP-like, had no effect. These data suggest that PCP is a potent, selective, noncompetitive inhibitor of amino acid-induced [3H]NE release and that this action of PCP is mediated through the PCP/sigma receptor.
我们之前曾报道，苯环己哌啶（PCP）可拮抗N-甲基-D-天冬氨酸（NMDA）诱导的大鼠纹状体和伏隔核切片中多巴胺和乙酰胆碱的释放。在本实验中，我们研究了PCP对NMDA和 kainic acid（KA）诱导的灌流大鼠海马切片中[3H]去甲肾上腺素（NE）释放的影响。NMDA和KA刺激NE流出，其EC50值分别为192和245 microM。缓冲液中存在1.2 mM MgCl2可消除NMDA诱导的释放，但对KA诱导的释放影响很小。PCP抑制100 microM NMDA诱导的[3H]NE释放，IC50为46 nM，但对300 microM KA刺激的NE释放无影响。2-氨基磷酸戊酸拮抗NMDA诱导的释放，使浓度-反应曲线平行右移。然而，PCP使浓度-反应曲线以非平行方式右移。具有PCP样特性的药物，如右吗拉胺和环唑辛，抑制NMDA诱导的释放，而相关药物如左吗拉胺、乙基酮环唑辛和吗啡，它们不是PCP样的，则无作用。这些数据表明，PCP是一种强效、选择性、非竞争性的氨基酸诱导的[3H]NE释放抑制剂，且PCP的这种作用是通过PCP/σ受体介导的。
