Elucidation of the transporters, and integration research of their molecular entities and activities for the drug transport in the brain and kidneys

本研究阐明了作为H+/有机阳离子交换的MATE介导小鼠中各种药物、内源性代谢产物（N-甲基烟酰胺）和荧光的尿排泄，并且MATE的抑制是西咪替丁和甲氧苄啶尿排泄中药物-药物相互作用的潜在机制的一部分。NPT 4介导各种阴离子药物如利尿剂在HEK 293细胞中的易化扩散。发现MCT 9在近端小管的基底外侧膜上表达。在经尿液排泄的药物中，OCT 2仅能识别亲水性化合物作为底物。MCT 9还作为有机阳离子转运蛋白，显示出与OCT 2不同的底物特异性。由于MCT 9也在血脑屏障中表达，因此推测MCT 9除参与肾脏外还参与药物在中枢神经系统中的处置。

This study elucidated that MATEs which act as H+/organic cation exchanges mediate the urinary excretion of various drugs, endogenous metabolite (N-methylnicotinamide) and fluorescents in mouse, and that inhibition of MATEs is part of the mechanism underlying the drug-drug interactions in the urinary excretion with cimetidine and trimethoprim. NPT4 mediates facilitated diffusion of various anionic drugs such as diuretics in HEK293 cells. MCT9 is found to be expressed on the basolateral membrane of the proximal tubules. Among the drugs which undergo urinary excretion, OCT2 can recognize only hydrophilic compounds as substrate. MCT9 also acts as organic cation transporter showing substrate specificity distinct from OCT2. Since MCT9 is also expressed in the blood-brain barrier, it is speculated that MCT9 is involved in the disposition of drugs in the central nervous system in addition to the kidney.