Matsubara K, Idzu T, Kobayashi Y, Gonda T, Okunishi H, Kimura K
Department of Legal Medicine, Shimane Medical University, Izumo, Japan.
Eur J Pharmacol. 1996 Nov 14;315(2):145-51. doi: 10.1016/s0014-2999(96)00630-9.
The effects of N-methyl-4-phenylpyridinium cation (MPP+) and of an endogenously formed analog, 2,9-di-methyl-norharmanium cation (2,9-Me2NH+), on extracellular dopamine were studied in the striatum of freely moving rats. Perfusion of either 2,9-Me2NH+ or MPP+ through a microdialysis probe evoked a marked and dose-dependent increase of dopamine levels. Tetrodotoxin and Ca(2+)-free medium prevented the increase in dopamine levels induced by 2,9-Me2NH+, but not that induced by MPP+. Cocaine, 3 microM, intensified the 2,9-Me2 NH(+)-induced increase in extracellular dopamine and slightly attenuated the MPP(+)-induced efflux. S(-)-3-(3-Hydroxy-phenyl)-N-propylpiperidine, that acts as an antagonist of dopamine autoreceptors in the presence of a dopamine reuptake inhibitor, markedly enhanced the increase in extracellular dopamine elicited by 2,9-Me2NH+, but not that by MPP+. These results suggested that 2,9-Me2NH+ was a potent dopamine reuptake blocker, whereas MPP+ acts as an amphetamine-like dopamine releaser rather than a reuptake inhibitor on the membrane transporter.
在自由活动大鼠的纹状体中，研究了N-甲基-4-苯基吡啶阳离子（MPP+）和内源性形成的类似物2,9-二甲基去氢骆驼蓬阳离子（2,9-Me2NH+）对细胞外多巴胺的影响。通过微透析探针灌注2,9-Me2NH+或MPP+均可引起多巴胺水平显著且呈剂量依赖性的升高。河豚毒素和无钙培养基可阻止2,9-Me2NH+诱导的多巴胺水平升高，但不能阻止MPP+诱导的升高。3微摩尔的可卡因可增强2,9-Me2NH+诱导的细胞外多巴胺升高，并略微减弱MPP+诱导的外流。S(-)-3-(3-羟基苯基)-N-丙基哌啶在多巴胺再摄取抑制剂存在下作为多巴胺自身受体的拮抗剂，可显著增强2,9-Me2NH+引起的细胞外多巴胺升高，但不能增强MPP+引起的升高。这些结果表明，2,9-Me2NH+是一种有效的多巴胺再摄取阻滞剂，而MPP+在膜转运体上的作用类似于苯丙胺样多巴胺释放剂，而非再摄取抑制剂。
