Physiological study on the transport functions at the blood-brain barrier relating to neural disorders.

该项目的目的是阐明与神经疾病相关的血脑屏障（BBB）转运蛋白的生理功能。BBB参与γ-氨基丁酸的脑-血外排转运，GAT 2/BGT-1介导该转运过程。BCEC还表达5-羟色胺和去甲肾上腺素转运蛋白。有机阴离子转运蛋白3（OAT 3）和ASCT 2定位于BCEC的近腔膜。OAT 3参与多巴胺代谢物、尿毒症毒素和硫嘌呤核碱基类似物的脑-血外排。ASCT 2在BBB的L-异构体选择性天冬氨酸外排转运中起作用。硫酸脱氢表雄酮和小分子中性氨基酸分别通过有机阴离子转运多肽2和ATA 2介导的脑-血外排转运。血脑屏障转运蛋白受多种因素的调节，ATA 2受渗透压的影响，牛磺酸转运蛋白受TNF-α的影响，L-胱氨酸/L-谷氨酸交换转运蛋白受氧化应激的影响。这些结果使我们对中枢神经系统疾病与血脑屏障功能的关系有了新的认识。

The purpose of the project was to clarify the physiological function of transporters at the blood-brain barrier (BBB) relating to neural disorders. The BBB is involved in the brain-to-blood efflux transport of γ-aminobutyric acid, and GAT2/BGT-1 mediates this transport process. BCECs also express serotonin and norepinephrine transporters. Organic anion transporter 3 (OAT3) and ASCT2 are localized at the abluminal membrane of the BCECs. OAT3 is involved in the brain-to-blood efflux of a dopamine metabolite, a uremic toxin and thiopurine nucleobase analogs. ASCT2 plays a role in L-isomer-selective aspartic acid efflux transport at the BBB. Dehydroepiandrosterone sulfate and small neutral amino acids undergo brain-to-blood efflux transport mediated by organic anion transporting polypeptide 2 and ATA2, respectively. The BBB transporters are regulated by various factors, ATA2 by osmolarity, taurine transporter by TNF-α, and L-cystine/L-glutamic acid exchange transporter by oxidative stress. These results gave us new understanding of the relationship between CNS disorders and BBB function.