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

多巴胺转运蛋白（DAT）的调节及其在神经元活动调节和神经元毒性发展中的作用在表达DAT的各种细胞系统中进行了研究。MPP^+诱导表达大鼠DAT cDNA的COS细胞（COS/DAT）和PC 12细胞死亡.利血平可增强MPP^+诱导的PC 12细胞死亡，而α-甲基-p-酪氨酸对MPP ^+诱导的PC 12细胞死亡无影响.吲哚美辛和布洛芬处理PC 12细胞可增强MPP^+诱导的细胞死亡，而阿司匹林和考克斯-2特异性抑制剂NS-398对MPP ^+诱导的细胞死亡无影响.高浓度的PPARγ配体导致细胞死亡.花生四烯酸可增强无BSA培养基中多巴胺的摄取。L-DOPA可促进COS/DAT细胞多巴胺摄取，L-系统抑制剂BCH不抑制L-DOPA的作用。在SK-N-SH细胞和PC 12细胞中，L-DOPA在低浓度下增强多巴胺摄取，在高浓度下降低摄取。左旋多巴抑制大鼠纹状体突触体对多巴胺的摄取，此作用可被BCH和芳香族氨基酸脱羧酶抑制剂阻断.局部麻醉药对单胺转运体有抑制作用，重复给药可引起小鼠点燃惊厥。重复给予去甲肾上腺素转运体抑制剂可增强利多卡因诱导的惊厥并减弱可卡因诱导的惊厥。SSRI在急性治疗中增强利多卡因惊厥，但慢性治疗效果不明显。这些结果揭示了多巴胺转运功能的一部分调节。

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.