Hanson Glen R, Gibb James W, Metzger Ryan R, Kokoshka Jerry M, Fleckenstein Annette E
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.
Ann N Y Acad Sci. 1998 May;844(1):103-107. doi: 10.1111/j.1749-6632.1998.tb08225.x.
Treatment with high doses of methamphetamine (METH) results in dramatic changes in extrapyramidal monoaminergic systems. Elevated concentrations of extracellular dopamine (DA), caused by METH administration, are thought to contribute to these effects due to the oxidative potential of this reactive catecholamine. According to this hypothesis monoaminergic cellular elements, which are vulnerable to oxidative modification, may be especially sensitive to high-dose METH treatments. We confirmed this possibility by observing that both tryptophan hydroxylase (the synthesizing enzyme for serotonin) and the DA transporter, proteins particularly susceptible to oxidative modification, were rapidly (within 30 min), but reversibly (returned to control levels by 36 hr) inactivated by a single administration of METH. These findings suggest that there also may be other cellular elements similarly altered by METH treatment due to oxidative mechanisms.
高剂量甲基苯丙胺（METH）治疗会导致锥体外系单胺能系统发生显著变化。METH给药导致细胞外多巴胺（DA）浓度升高，由于这种活性儿茶酚胺的氧化潜能，人们认为这是造成这些影响的原因。根据这一假说，易受氧化修饰影响的单胺能细胞成分可能对高剂量METH治疗特别敏感。我们通过观察发现，色氨酸羟化酶（血清素合成酶）和DA转运体这两种特别易受氧化修饰的蛋白质，在单次给予METH后迅速（30分钟内）但可逆地（36小时后恢复到对照水平）失活，从而证实了这种可能性。这些发现表明，由于氧化机制，可能还有其他细胞成分会因METH治疗而发生类似改变。
