Molecular characterization of human and rat organic anion transporter OATP-D.
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-l/rlst-1, the rat oatp family, the prostaglandin transporter, and moatl/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,, 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.
Adachi
Hisanobu
H
Division of Gastroenterological Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seriyo-cho, Aoba-ku, Sendai 980-8574, Japan.
Suzuki
Takehiro
T
Abe
Michiaki
M
Asano
Naoki
N
Mizutamari
Hiroya
H
Tanemoto
Masayuki
M
Nishio
Toshiyuki
T
Onogawa
Tohru
T
Toyohara
Takafumi
T
Kasai
Satoshi
S
Satoh
Fumitoshi
F
Suzuki
Masanori
M
Tokui
Taro
T
Unno
Michiaki
M
Shimosegawa
Tooru
T
Matsuno
Seiki
S
Ito
Sadayoshi
S
Abe
Takaaki
T
D000527:Alprostadil / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000378:metabolism; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000502:physiology; D002051:Burkitt Lymphoma; D018076:DNA, Complementary; D015232:Dinoprostone / Q000378:metabolism*; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D007945:Leukemia, Lymphoid; D008175:Lung Neoplasms; D008545:Melanoma; D008969:Molecular Sequence Data; D009865:Oocytes; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014982:Xenopus laevis
D000838:Anions; D018076:DNA, Complementary; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C479544:SLCO3A1 protein, human; C479545:Slco3a1 protein, rat; D000527:Alprostadil; D015232:Dinoprostone