DIFFERENTIAL EXPRESSION OF MULTIDRUG-RESISTANCE (MDR) AND CANALICULARMULTISPECIFIC ORGANIC ANION TRANSPORTER (CMOAT) GENES FOLLOWING EXTRAHEPATIC BILIARY OBSTRUCTION IN RATS

Citation
T. Kagawa et al., DIFFERENTIAL EXPRESSION OF MULTIDRUG-RESISTANCE (MDR) AND CANALICULARMULTISPECIFIC ORGANIC ANION TRANSPORTER (CMOAT) GENES FOLLOWING EXTRAHEPATIC BILIARY OBSTRUCTION IN RATS, Biochemistry and molecular biology international, 44(3), 1998, pp. 443-452
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
1039-9712
Volume
44
Issue
3
Year of publication
1998
Pages
443 - 452
Database
ISI
SICI code
1039-9712(1998)44:3<443:DEOM(A>2.0.ZU;2-I
Abstract
The hepatic canalicular membrane has transporters that play an importa nt role as efflux pumps in the excretion of endogenous bile constituen ts or xenobiotics into bile canaliculi. To elucidate functional signif icance of canalicular transporters in the mechanism of cholestasis, mR NA expression levels of multidrug resistance (mdr) Ib, mdr2 and canali cular multispecific organic anion transporter (cMOAT) genes were analy zed by Southern blotting of reverse-transcribed PCR products of liver mRNA obtained from cholestatic rats that had been subjected to bile du ct ligation. Both mdr1b and mdr2 mRNA expression increased after ligat ion. Immunohistochemical study revealed that the products of both mdr1 b and mdr2 were present on the canaliculi, and that their levels incre ased after ligation. In contrast, cMOAT mRNA expression was not increa sed, but rather attenuated by ligation. The expression of canalicular transporters was differentially regulated in extrahepatic biliary obst ruction, indicating the different roles are played by mdr and cMOAT in the pathogenesis of cholestasis.