Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins.
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.
Kimura
Hiroaki
H
Division of Nephrology and Hypertension, Department of Internal Medicine, Jikeikai University School of Medicine, Tokyo, Japan.
Takeda
Michio
M
Narikawa
Shinichi
S
Enomoto
Atsushi
A
Ichida
Kimiyoshi
K
Endou
Hitoshi
H
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D011453:Prostaglandins; C427207:SLC22A11 protein, human; C491013:SLC22A2 protein, human; C490280:SLC22A7 protein, human; C491012:Slc22a2 protein, mouse; C490281:Slc22a7 protein, mouse; C114338:organic anion transport protein 3; D015237:Dinoprost; D015232:Dinoprostone