Nabeshima T, Ishikawa K, Yamaguchi K, Furukawa H, Kameyama T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Biochem Pharmacol. 1988 Sep 1;37(17):3277-83. doi: 10.1016/0006-2952(88)90639-9.
We investigated whether phencyclidine (PCP)-induced head-twitch was antagonized in rats by ritanserin, a selective serotonin2 (5-HT2) receptor antagonist, to confirm the involvement of 5-HT neurons in PCP action and to discover whether PCP could protect the binding sites of [3H]PCP and [3H]ketanserin from the inhibitory effect of protein-modifying reagents which affect sulfhydryl groups. PCP (7.5, 10 and 12.5 mg/kg, i.p.)-induced head-twitch was completely antagonized by ritanserin (1 mg/kg, s.c.). Scatchard plots of specific [3H]PCP and [3H]ketanserin binding showed that sulfhydryl-modifying reagent, N-ethylmaleimide (NEM, 100 microM) caused a significant decrease in Bmax without changing Kd. PCP (10 microM) and ritanserin (1 microM) protected [3H]PCP and [3H]ketanserin binding sites from the decrease in the number induced by NEM (100 microM). 5-HT protected [3H]5-HT binding sites from inactivation by NEM, but PCP and ritanserin did not show any effect. On the basis of the present findings, it is concluded that PCP can interact with 5-HT2 receptors directly or allosterically, and 5-HT2 receptors may locate at PCP binding sites in membranes.
我们研究了选择性5-羟色胺2（5-HT2）受体拮抗剂利坦色林是否能拮抗苯环利定（PCP）诱导的大鼠头部抽搐，以证实5-羟色胺能神经元参与PCP的作用，并探究PCP是否能保护[3H]PCP和[3H]酮色林的结合位点免受影响巯基的蛋白质修饰试剂的抑制作用。PCP（7.5、10和12.5毫克/千克，腹腔注射）诱导的头部抽搐被利坦色林（1毫克/千克，皮下注射）完全拮抗。特异性[3H]PCP和[3H]酮色林结合的Scatchard图显示，巯基修饰试剂N-乙基马来酰亚胺（NEM，100微摩尔）导致Bmax显著降低，而Kd不变。PCP（10微摩尔）和利坦色林（1微摩尔）保护[3H]PCP和[3H]酮色林结合位点免受NEM（100微摩尔）诱导的数量减少。5-羟色胺保护[3H]5-羟色胺结合位点免受NEM的失活作用，但PCP和利坦色林未显示任何作用。基于目前的研究结果，得出结论：PCP可直接或变构地与5-HT2受体相互作用，且5-HT2受体可能位于细胞膜中的PCP结合位点处。
