Brooks W J, Jarvis M F, Wagner G C
Department of Psychology, Rutgers State University, New Brunswick, New Jersey.
J Neural Transm. 1988;71(2):85-90. doi: 10.1007/BF01245250.
Monoamine oxidase-B (MAO-B) has been determined to be the enzyme responsible for the conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into its toxic metabolite 1-methyl-4-phenylpyridine ion (MPP+). Since this enzyme has been localized primarily in astrocytes and serotonergic neurons, it would appear that MPP+ is being produced outside the dopaminergic neurons. To investigate this possibility, the administration of MPTP was preceded by systemically administered fluoxetine. In keeping with its demonstrated ability to inhibit uptake into serotonergic neurons and serotonin uptake into astrocytes, fluoxetine pretreatment resulted in a significant attenuation of MPTP-induced depletions of striatal dopamine and serotonin concentration. These results support the extra-dopaminergic production of MPP+.
已确定单胺氧化酶B（MAO-B）是负责将1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）转化为其有毒代谢物1-甲基-4-苯基吡啶离子（MPP+）的酶。由于该酶主要定位于星形胶质细胞和血清素能神经元中，因此MPP+似乎是在多巴胺能神经元之外产生的。为了研究这种可能性，在给予MPTP之前先全身给予氟西汀。与它已被证实的抑制血清素能神经元摄取和5-羟色胺摄取到星形胶质细胞的能力一致，氟西汀预处理导致MPTP诱导的纹状体多巴胺和血清素浓度耗竭显著减轻。这些结果支持MPP+的多巴胺能外生成。
