Expression, transport properties, and chromosomal location of organic anion transporter subtype 3.
The rat and mouse organic anion-transporting polypeptides (oatp) subtype 3 (oatp3) were cloned to further define components of the intestinal bile acid transport system. In transfected COS cells, oatp3 mediated Na(+)-independent, DIDS-inhibited taurocholate uptake (Michaelis-Menten constant approximately 30 microM). The oatp3-mediated uptake rates and affinities were highest for glycine-conjugated dihydroxy bile acids. In stably transfected, polarized Madin-Darby canine kidney (MDCK) cells, oatp3 mediated only apical uptake of taurocholate. RT-PCR analysis revealed that rat oatp3, but not oatp1 or oatp2, was expressed in small intestine. By RNase protection assay, oatp3 mRNA was readily detected down the length of the small intestine as well as in brain, lung, and retina. An antibody directed to the carboxy terminus localized oatp3 to the apical brush-border membrane of rat jejunal enterocytes. The mouse oatp3 gene was localized to a region of mouse chromosome 6. This region is syntenic with human chromosome 12p12, where the human OATP-A gene was mapped, suggesting that rodent oatp3 is orthologous to the human OATP-A. These transport and expression properties suggest that rat oatp3 mediates the anion exchange-driven absorption of bile acids previously described for the proximal small intestine.
Walters
H C
HC
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Craddock
A L
AL
Fusegawa
H
H
Willingham
M C
MC
Dawson
P A
PA
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D001483:Base Sequence; D001646:Bile / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000493:pharmacokinetics; D002875:Chromosomes; D004285:Dogs; D006801:Humans; D007422:Intestines / Q000737:chemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D029362:Organic Anion Transporters, Sodium-Independent; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012964:Sodium / Q000378:metabolism
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid