Kramer H K, Poblete J C, Azmitia E C
Department of Biology, New York University, NY 10003, USA.
Brain Res. 1995 May 22;680(1-2):1-8. doi: 10.1016/0006-8993(95)00199-z.
The metabolic effects of the neurotoxic, ring-substituted amphetamine 3,4-methylenedioxy-methamphetamine (MDMA or 'Ecstasy') were examined in vivo. In this study, we focused on the ability of MDMA to induce a translocation of the calcium and phospholipid-dependent protein kinase C (PKC) from the cytosol to the cortical plasma membrane. Two injections of MDMA (20 mg/kg; 10 h apart; s.c.) increased the density of membrane bound PKC sites by 48.0% over saline treated animals without mediating a significant change in ligand ([3H]phorbol 12,13 dibutyrate; [3H]PDBu) affinity. Longer drug treatments (8 x 20 mg/kg) induced a lasting (up to 5 days post-treatment) increase in the density of membrane-bound PKC. Prior destruction of cortical 5-HT nerve terminals with p-chloroamphetamine (PCA) prevents this effect and suggests that viable 5-HT uptake sites are essential for MDMA-induced PKC translocation. These results demonstrate that MDMA-induced PKC translocation is mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.
在体内研究了神经毒性的环取代苯丙胺3,4-亚甲基二氧基甲基苯丙胺（MDMA或“摇头丸”）的代谢作用。在本研究中，我们重点关注MDMA诱导钙和磷脂依赖性蛋白激酶C（PKC）从胞质溶胶转位至皮质质膜的能力。两次注射MDMA（20mg/kg；间隔10小时；皮下注射）使膜结合PKC位点的密度比盐水处理的动物增加了48.0%，而未介导配体（[3H]佛波醇12,13-二丁酸酯；[3H]PDBu）亲和力的显著变化。更长时间的药物处理（8×20mg/kg）导致膜结合PKC密度持续增加（治疗后长达5天）。事先用对氯苯丙胺（PCA）破坏皮质5-羟色胺（5-HT）神经末梢可防止这种效应，并表明存活的5-HT摄取位点对于MDMA诱导的PKC转位至关重要。这些结果表明，MDMA诱导的PKC转位由存活的皮质5-HT神经末梢介导，并且激酶的长期激活可能导致MDMA诱导的5-羟色胺能神经毒性。
