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Am J Physiol Renal Physiol 285: F1188-F1197, 2003. First published August 19, 2003; doi:10.1152/ajprenal.00402.2002
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Molecular characterization of human and rat organic anion transporter OATP-D

Hisanobu Adachi,1,* Takehiro Suzuki,2,* Michiaki Abe,2,* Naoki Asano,3 Hiroya Mizutamari,3 Masayuki Tanemoto,2 Toshiyuki Nishio,4 Tohru Onogawa,1 Takafumi Toyohara,2 Satoshi Kasai,2 Fumitoshi Satoh,2 Masanori Suzuki,1 Taro Tokui,5 Michiaki Unno,1 Tooru Shimosegawa,3 Seiki Matsuno,1 Sadayoshi Ito,2 and Takaaki Abe2,6

1Division of Gastroenterological Surgery, Department of Surgery, Divisions of 2Nephrology, Endocrinology, and Vascular Medicine, and 3Gastroenterology, Department of Medicine, and 4Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai 980-8574; 5Analytical and Metabolic Research Laboratories, Sankyo Company, Limited, Tokyo 140-8710; and 6PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan

Submitted 13 November 2002 ; accepted in final form 13 July 2003

We have isolated and characterized a novel human and rat organic anion transporter subtype, OATP-D. The isolated cDNA from human brain encodes a polypeptide of 710 amino acids (Mr 76,534) with 12 predicted transmembrane domains. The rat clone encodes 710 amino acids (Mr 76,821) with 97.6% amino acid sequence homology with human OATP-D. Human and rat OATP-D have moderate amino acid sequence homology with LST-1/rlst-1, the rat oatp family, the prostaglandin transporter, and moat1/MOAT1/KIAA0880/OATP-B. Phylogenetic tree analysis revealed that OATP-D is branched in a different position from all known organic anion transporters. OATP-D transports prostaglandin E1 (Km 48.5 nM), prostaglandin E2 (Km 55.5 nM), and prostaglandin F2{alpha}, suggesting that, functionally, OATP-D encodes a protein that has similar characteristics to those of the prostaglandin transporter. Rat OATP-D also transports prostaglandins. The expression pattern of OATP-D mRNA was abundant mainly in the heart, testis, brain, and some cancer cells. Immunohistochemical analysis further revealed that rat OATP-D is widely expressed in the vascular, renal, and reproductive system at the protein level. These results suggest that OATP-D plays an important role in translocating prostaglandins in specialized tissues and cells.

prostaglandin transporter; eicosanoid



Address for reprint requests and other correspondence: T. Abe, Div. of Nephrology, Endocrinology, and Vascular Medicine, Dept. of Medicine, Tohoku Univ. Graduate School of Medicine, 1-1 Seriyo-cho, Aoba-ku, Sendai 980-8574, Japan (E-mail: takaaki{at}mail.tains.tohoku.ac.jp).




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