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MATEs介导多种药物、内源性代谢物（n -甲基烟酰胺）和荧光剂在小鼠尿排泄中的作用，并且对MATEs的抑制是西咪替丁和甲氧苄啶尿排泄中药物-药物相互作用的机制之一。NPT4介导多种阴离子药物如利尿剂在HEK293细胞中的扩散。发现MCT9在近端小管的基底外膜上表达。在尿排泄的药物中，OCT2只能识别亲水化合物作为底物。MCT9也作为有机阳离子转运体，表现出与OCT2不同的底物特异性。由于MCT9也在血脑屏障中表达，推测MCT9除参与肾脏外，还参与中枢神经系统的药物处置。

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.