Publications

• Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins.

  Kimura H., Takeda M., Narikawa S., Enomoto A., Ichida K., Endou H.

  Prostaglandin E(2) (PGE(2)) and prostaglandin F(2 alpha) (PGF(2 alpha)) have been used for the induction of labor and the termination of pregnancy. Renal excretion is shown to be an important pathway for the elimination of PGE(2) and PGF(2 alpha). The purpose of this study was to elucidate the mol ... >> More

  Prostaglandin E(2) (PGE(2)) and prostaglandin F(2 alpha) (PGF(2 alpha)) have been used for the induction of labor and the termination of pregnancy. Renal excretion is shown to be an important pathway for the elimination of PGE(2) and PGF(2 alpha). The purpose of this study was to elucidate the molecular mechanism of renal PGE(2) and PGF(2 alpha) transport using cells stably expressing human organic anion transporter (hOAT) 1, hOAT2, hOAT3, and hOAT4, and human organic cation transporter (hOCT) 1 and hOCT2. A time- and dose-dependent increase in PGE(2) and PGF(2 alpha) uptake was observed in cells expressing hOAT1, hOAT2, hOAT3, hOAT4, hOCT1, and hOCT2. The K(m) values of PGE(2) uptake by hOAT1, hOAT2, hOAT3, hOAT4, hOCT1, and hOCT2 were 970, 713, 345, 154, 657, and 28.9 nM, respectively, whereas those of PGF(2 alpha) uptake by hOAT1, hOAT3, hOAT4, hOCT1, and hOCT2 were 575, 1092, 692, 477, and 334 nM, respectively. PGE(2) and PGF(2 alpha) significantly inhibited organic anion uptake by hOATs and organic cation uptake by hOCTs. In conclusion, considering the localization of these transporters, the results suggest that PGE(2) and PGF(2 alpha) transport in the basolateral membrane of the proximal tubule is mediated by multiple pathways including hOAT1, hOAT2, hOAT3, and hOCT2, whereas that in the apical side is mediated by hOAT4. << Less

  J. Pharmacol. Exp. Ther. 301:293-298(2002) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Expression cloning and characterization of a novel multispecific organic anion transporter.

  Sekine T., Watanabe N., Hosoyamada M., Kanai Y., Endou H.

  Numerous drugs and endogenous compounds are efficiently excreted from the renal proximal tubule via carrier-mediated pathways. Transepithelial excretion of organic anions occurs via their accumulative transport from the blood into the proximal tubule cells across the basolateral membrane and subse ... >> More

  Numerous drugs and endogenous compounds are efficiently excreted from the renal proximal tubule via carrier-mediated pathways. Transepithelial excretion of organic anions occurs via their accumulative transport from the blood into the proximal tubule cells across the basolateral membrane and subsequent secretion into the urine through the apical membrane. Here we report on the isolation of a novel complementary DNA from rat kidney that encodes a 551-amino acid residue protein (OAT1) with 12 putative membrane-spanning domains. When expressed in Xenopus laevis oocytes, OAT1 mediated sodium-independent para-aminohippurate (PAH) uptake (Km = 14.3 +/-2.9 microM). The uptake rate of PAH was increased by the outwardly directed dicarboxylate gradient, consisting with the idea that OAT1 is an organic anion/dicarboxylate exchanger. OAT1 displayed remarkably wide substrate selectivity, covering endogenous substrates such as cyclic nucleotides, a prostaglandin and uric acid, and a variety of drugs with different structures (e.g. antibiotics, a nonsteroidal anti-inflammatory drug, diuretics, an antineoplastic drug, and a uricosuric drug). The Northern blot analysis and in situ hybridization revealed that OAT1 is exclusively expressed in the particular segment of the proximal tubule in the kidney. These data suggest that OAT1 is a multispecific organic anion transporter at the basolateral membrane of the proximal tubule. Isolation of OAT1 will facilitate elucidation of the molecular basis of drug kinetics and the development of new drugs lacking unwanted side effects. << Less

  J. Biol. Chem. 272:18526-18529(1997) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.