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

Prostaglandin E-2 (PGE(2)) and prostaglandin F-2alpha (PGF(2alpha)) 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(2alpha). The purpose of this study was to elucidate the molecular mechanism of renal PGE2 and PGF(2alpha) 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(2alpha) 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(2alpha) uptake by hOAT1, hOAT3, hOAT4, hOCT1, and hOCT2 were 575, 1092, 692, 477, and 334 nM, respectively. PGE(2) and PGF(2alpha) 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(2alpha) 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.