Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney

作者: Tsuneo Deguchi , Sumio Ohtsuki , Masaki Otagiri , Hitomi Takanaga , Hiroshi Asaba

DOI: 10.1046/J.1523-1755.2002.00318.X

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摘要: Major role of organic anion transporter 3 in the transport indoxyl sulfate kidney. Background Indoxyl is a uremic toxin that accumulates body because patient's inability to excrete it and induces number symptoms leads chronic renal failure. The functional failure excretion system for causes its accumulation blood. purpose present study was characterize mechanism responsible sulfate. Methods [ H]indoxyl investigated using an vivo tissue-sampling single-injection technique, kidney uptake index (KUI) method. Rat (rOAT3)-expressing Xenopus laevis oocyte used measuring activity. Results Probenecid showed concentration-dependent inhibitory effect on KUI method, inhibited by anions such as para -aminohippuric acid (PAH) benzylpenicillin, weak base cimetidine, toxins, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic (CMPF) hippuric (HA). However, salicylic acid, indomethacin, 3,5,3′-triiodo-L-thyronine indole acetic (IA) had no uptake. rOAT3-expressing oocytes exhibited rOAT3 (K m = 158 μmol/L). Moreover, toxins rOAT3. Conclusions These results suggest sulfate, share Mutual inhibition these via OAT3 may accelerate their and, thereby, progression nephrotoxicity uremia.

参考文章(42)
Ise M, Niwa T, Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. Journal of Laboratory and Clinical Medicine. ,vol. 124, pp. 96- 104 ,(1994)
T Miyazaki, K Endo, M Ise, M Hirata, Y Ito, T Niwa, H Seo, Indoxyl sulfate stimulates renal synthesis of transforming growth factor-beta 1 and progression of renal failure. Kidney International. ,vol. 63, ,(1997)
Toshiaki Sakai, Keishi Yamasaki, Tomoko Sako, Ulrich Kragh‐Hansen, Ayaka Suenaga, Masaki Otagiri, Interaction mechanism between indoxyl sulfate, a typical uremic toxin bound to site II, and ligands bound to site I of human serum albumin. Pharmaceutical Research. ,vol. 18, pp. 520- 524 ,(2001) , 10.1023/A:1011014629551
Alan L. Goldin, Maintenance of Xenopus laevis and oocyte injection. Methods in Enzymology. ,vol. 207, pp. 266- 279 ,(1992) , 10.1016/0076-6879(92)07017-I
Arthit Chairoungdua, Hitoshi Endou, Nopporn Apiwattanakul, Takashi Sekine, Samaisukh Sophasan, Yoshikatsu Kanai, Noriko Nakajima, Transport Properties of Nonsteroidal Anti-Inflammatory Drugs by Organic Anion Transporter 1 Expressed in Xenopus laevisOocytes Molecular Pharmacology. ,vol. 55, pp. 847- 854 ,(1999)
Ken Ichi Inui, Hideyuki Saito, Satohiro Masuda, Koji Ibaramoto, Ayako Takeuchi, Yukiya Hashimoto, Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney. Molecular Pharmacology. ,vol. 55, pp. 743- 752 ,(1999)
Bo Feng, Mark J. Dresser, Yan Shu, Susan Jean Johns, Kathleen M. Giacomini, Arginine 454 and Lysine 370 Are Essential for the Anion Specificity of the Organic Anion Transporter, rOAT3† Biochemistry. ,vol. 40, pp. 5511- 5520 ,(2001) , 10.1021/BI002841O
Yoshiyuki Yoshida, Agnes Fogo, Iekuni Ichikawa, Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis Kidney International. ,vol. 35, pp. 654- 660 ,(1989) , 10.1038/KI.1989.35
Toshiaki SAKAI, Akira TAKADATE, Masaki OTAGIRI, Characterization of Binding Site of Uremic Toxins on Human Serum Albumin Biological & Pharmaceutical Bulletin. ,vol. 18, pp. 1755- 1761 ,(1995) , 10.1248/BPB.18.1755