Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1.
OBJECTIVE
Recently, we isolated a new complementary DNA (cDNA) encoding human liver-specific organic anion transporter (LST-1), representing the multispecificity of human liver. The aim of this study was to isolate a rat counterpart of human LST-1 and examine the expression regulation of its messenger RNA (mRNA) to clarify the molecular basis of cholestasis.


METHODS
A rat liver cDNA library was screened with human LST-1 cDNA as a probe. Xenopus oocyte expression system was used for functional analysis. Northern blot analyses were performed using the isolated cDNA (termed rlst-1). The bile duct ligation model and the cecum ligation and puncture model were used for expression analyses.


RESULTS
rlst-1 encodes 652 amino acids, predicting at least 11 transmembrane regions. The overall homology with human LST-1 was 60.2%, which is the highest among all known organic anion transporters. rlst-1 also belongs to the same new gene family as human LST-1, located between the organic anion transporter family and the prostaglandin transporter. rlst-1 preferably transports taurocholate (K(m), 9.45 micromol/L) in an Na(+)-independent manner. The rlst-1 mRNA is exclusively expressed in the liver. In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated.


CONCLUSIONS
rlst-1 is a counterpart of human LST-1 and is one of the important transporters in rat liver for the clearance of bile acid. The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.
Kakyo
M
M
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Ltd., Tokyo, Japan.
Unno
M
M
Tokui
T
T
Nakagomi
R
R
Nishio
T
T
Iwasashi
H
H
Nakai
D
D
Seki
M
M
Suzuki
M
M
Naitoh
T
T
Matsuno
S
S
Yawo
H
H
Abe
T
T
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D027321:Anion Transport Proteins; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D002432:Cecum; D002779:Cholestasis / Q000209:etiology / Q000235:genetics; D003135:Common Bile Duct; D005246:Feedback; D005260:Female; D005786:Gene Expression Regulation; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes; D011677:Punctures; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014982:Xenopus laevis
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D012333:RNA, Messenger