Kokoshka J M, Vaughan R A, Hanson G R, Fleckenstein A E
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
Eur J Pharmacol. 1998 Nov 20;361(2-3):269-75. doi: 10.1016/s0014-2999(98)00741-9.
The nature of methamphetamine-induced rapid and transient decreases in dopamine transporter activity was investigated. Regional specificity was demonstrated, since [3H]dopamine uptake was decreased in synaptosomes prepared from the striatum, but not nucleus accumbens, of methamphetamine-treated rats. Differences among effects on dopamine transporter activity and ligand binding were also observed, since a single methamphetamine administration decreased [3H]dopamine uptake without altering [3H]WIN35428 (3H-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate) binding in synaptosomes prepared 1 h after injection. Moreover, multiple methamphetamine injections caused a greater decrease in [3H]dopamine uptake than [3H]WIN35428 binding in synaptosomes prepared I h after dosing. Finally, decreases in [3H]dopamine uptake, but not [3H]WIN35428 binding, were partially reversed 24 h after multiple methamphetamine injections. Western blotting indicated that saline- and methamphetamine-affected dopamine transporters co-migrated on sodium dodecyl sulfate (SDS) gels at approximately 80 kDa, and that acute, methamphetamine-induced decreases in [3H]dopamine uptake were not due to loss of dopamine transporter protein. These findings demonstrate heretofore-uncharacterized features of the acute effect of methamphetamine on dopamine transporters.
研究了甲基苯丙胺引起的多巴胺转运体活性快速和短暂降低的性质。由于在甲基苯丙胺处理的大鼠纹状体而非伏隔核制备的突触体中，[3H]多巴胺摄取减少，因此证明了区域特异性。还观察到对多巴胺转运体活性和配体结合的影响存在差异，因为单次给予甲基苯丙胺可降低[3H]多巴胺摄取，而不改变注射后1小时制备的突触体中[3H]WIN35428（3H-2-β-甲氧羰基-3-β-(4-氟苯基)托烷1,5-萘二磺酸盐）的结合。此外，多次注射甲基苯丙胺后，给药后1小时制备的突触体中[3H]多巴胺摄取的降低比[3H]WIN35428结合的降低更大。最后，多次注射甲基苯丙胺24小时后，[3H]多巴胺摄取的降低（而非[3H]WIN35428结合的降低）部分得到逆转。蛋白质印迹表明，生理盐水和甲基苯丙胺影响的多巴胺转运体在十二烷基硫酸钠（SDS）凝胶上共迁移，迁移位置约为80 kDa，且急性甲基苯丙胺诱导的[3H]多巴胺摄取降低并非由于多巴胺转运体蛋白的丢失。这些发现揭示了甲基苯丙胺对多巴胺转运体急性作用迄今未被描述的特征。
