TY - JOUR
T1 - Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1
AU - Kakyo, M.
AU - Unno, M.
AU - Tokui, T.
AU - Nakagomi, R.
AU - Nishio, T.
AU - Iwasashi, H.
AU - Nakai, D.
AU - Seki, M.
AU - Suzuki, M.
AU - Naitoh, T.
AU - Matsuno, S.
AU - Yawo, H.
AU - Abe, T.
N1 - Funding Information:
Supported in part by research grants from the Ministry of Education, Science, and Culture of Japan; Yamanouchi Foundation for Research on Metabolic Disorders; Nishimiya Foundation; Tokyo Biochemical Research Foundation; Japan Research Foundation for Clinical Pharmacology; Yokoyama Foundation for Clinical Pharmacology; Japan Health Sciences Foundation; and Inamori Foundation.
PY - 1999
Y1 - 1999
N2 - Background and Aims: 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 μmol/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.
AB - Background and Aims: 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 μmol/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.
UR - http://www.scopus.com/inward/record.url?scp=0032869932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032869932&partnerID=8YFLogxK
U2 - 10.1016/S0016-5085(99)70333-1
DO - 10.1016/S0016-5085(99)70333-1
M3 - Article
C2 - 10500057
AN - SCOPUS:0032869932
VL - 117
SP - 770
EP - 775
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 4
ER -