Fleckenstein A E, Wilkins D G, Gibb J W, Hanson G R
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
J Pharmacol Exp Ther. 1997 Oct;283(1):281-5.
Administration of a single high dose of methamphetamine (METH) causes a rapid and reversible decrease in the activity of the tryptophan hydroxylase (TPH), the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine. This effect can be reversed completely by exposing the METH-impaired enzyme to a reducing environment, which suggests that the decrease in TPH activity is a reversible oxidative consequence of free radical formation. Consistent with this hypothesis, a single METH administration to male rats increased oxygen radical formation, as demonstrated by increased striatal dihydroxybenzoic acid formation after coadministration of salicylate with METH. Prevention of METH-induced hyperthermia attenuated both the increase in dihydroxybenzoic acid formation and the decrease in TPH activity observed 1 h after METH administration. These data suggest that both reactive oxygen species and hyperthermia contribute to the acute decrease in TPH activity which results from a single METH administration.
单次给予高剂量甲基苯丙胺（METH）会导致色氨酸羟化酶（TPH）的活性迅速且可逆地降低，TPH是5-羟色胺合成中的限速酶。将受METH损害的酶置于还原环境中，这种效应可完全逆转，这表明TPH活性的降低是自由基形成的可逆氧化结果。与该假设一致的是，对雄性大鼠单次给予METH会增加氧自由基的形成，这可通过在给予METH的同时给予水杨酸盐后纹状体二羟基苯甲酸形成增加来证明。预防METH诱导的体温过高可减弱在给予METH 1小时后观察到的二羟基苯甲酸形成增加和TPH活性降低。这些数据表明，活性氧和体温过高均导致单次给予METH后TPH活性的急性降低。
