Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 102, Issue 9, Pages 3302-3308Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.23567
Keywords
active transport; renal excretion; membrane transporter; drug transport; organic anion transporter; organic cation transporter; elimination; renal clearance; multidrug and toxin extrusion
Funding
- Japan Society for the Promotion of Science (JSPS)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [25460231, 25670074, 23390138] Funding Source: KAKEN
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Organic anion transporters (OATs) and organic cation transporters (OCT) play pivotal roles in the uptake of drugs into epithelial cells at the basolateral membranes, and multidrug and toxin extrusion (MATE) mediates drug secretion into urine at the brush-border membranes. In this study, the expression and distribution of apical MATE1 and MATE2-K, and basolateral OAT1, OAT3, and OCT2 were compared using serial sections of human kidney cortex. First, mRNA expression in the proximal tubules was evaluated using laser microdissection. Levels of OAT, OCT2, and MATE mRNA in the proximal tubules were greatly higher compared with glomerulus. The results quantitatively indicated that these transporters were localized to proximal tubules in the renal cortex. Second, MATE1 and MATE2-K protein were detected in proximal epithelial cells in which OCT2 protein was expressed at the basolateral membranes. In addition, MATE1 was expressed at the brush-border membranes of tubular epithelial cells in which OAT1 and OAT3 were expressed. The results confirmed that OAT1, OAT3, OCT2, MATE1, and MATE2-K were coexpressed in tubular epithelial cells. The cooperation among OAT, OCT, and MATE in renal drug secretion was consistent with their distribution. (C) 2013 Wiley Periodicals, Inc.
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