Regulation of dopamine transporter function and its role in neuronal diseases - Regulation by arachidonic acid.

在表达DAT的不同细胞系统中，研究了多巴胺转运体(DAT)的调节及其在调节神经元活动和神经元毒性发展中的作用。结论：1.MPP~+可诱导表达大鼠DAT基因的COS细胞(COS/DAT)和PC-12细胞死亡。利血平和α-甲基-对酪氨酸处理PC-12细胞可增强MPP~+诱导的细胞死亡，但不影响细胞死亡。吲哚美辛和布洛芬处理PC12细胞可增强MPP^+诱导的细胞死亡，而阿司匹林和COX-2的特异性抑制剂NS-398对细胞死亡无影响。PPARγ的配体在高浓度时会引起细胞死亡。花生四烯酸促进无BSA培养基多巴胺摄取。L多巴可促进COS/DAT对多巴胺的摄取。L-多巴的作用不被L系统的阻断剂BCH所抑制。L多巴在低浓度时促进SK-N-SH细胞和PC12细胞对多巴胺的摄取，而在高浓度时则降低对多巴胺的摄取。L多巴可抑制大鼠纹状体突触体的多巴胺摄取，该作用可被BCH和芳香族氨基酸脱羧酶抑制剂阻断。局麻药对单胺转运体有抑制作用，反复给药可引起小鼠点燃惊厥。反复给予去甲肾上腺素转运体抑制剂可增强利多卡因诱发的惊厥和减轻可卡因诱发的惊厥。SSRI在急性治疗时可增加利多卡因惊厥的发生率，而在慢性治疗时作用不大。这些结果揭示了多巴胺转运功能的部分调节。

Regulation of dopamine transporter (DAT) and its role in the regulation of neuronal activities and the development of neuronal toxicities were studied in various cell systems expressing DAT.1. MPP^+ induced cell death in COS cells expressing rat DAT cDNA (COS/DAT) and in PC 12 cells.2. Treatment of PC 12 cells with reserpine enhanced MPP^+-induced cell death and α-methyl-p-tyrosine did not affect the cell death.3. Treatment of PC12 cells with indomethacin and ibuprofen enhanced MPP^+-induced cell death but aspirin and NS-398, an specific inhibitor of COX-2 did not affect the cell death.4. Ligands for PPARγ produced cell death with high concentrations.5. Arachidonic acid enhanced dopamine uptake in BSA free-medium.6. L-DOPA enhanced dopamine uptake in COS/DAT. The effect of L-DOPA was not inhibited by BCH, an inhibitor of L-system.7. L-DOPA enhanced dopamine uptake at low concentrations and reduced the uptake at high concentrations in SK-N-SH cells and PC 12 cells.8. L-DOPA inhibited dopamine uptake in rat striatum synaptosomes and the effect was blocked by BCH, and the inhibitors of aromatic amino acid decarboxylase.9. Local anesthetics exhibiting inhibitory action on monoamine transporter produced kindling convulsions by repeated administrations in mice. Repeated administration of norepinephrine transporter inhibitors enhanced lidocaine-induced convulsions and attenuated cocaine-induced convulsions. SSRI enhanced lidocaine-convulsions in acute treatment but little effect by the chronic treatment. These results revealed a part of regulation of dopamine transport function.