EXPRESSION OF A PUTATIVE ATP-BINDING CASSETTE REGION, HOMOLOGOUS TO THAT IN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP), IS HEREDITARILY DEFECTIVE IN EISAI HYPERBILIRUBINEMIC RATS (EHBR)

Citation
K. Ito et al., EXPRESSION OF A PUTATIVE ATP-BINDING CASSETTE REGION, HOMOLOGOUS TO THAT IN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP), IS HEREDITARILY DEFECTIVE IN EISAI HYPERBILIRUBINEMIC RATS (EHBR), HEPATOLOGY RESEARCH, 4(5), 1996, pp. 291-298
Citations number
20
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
13866346
Volume
4
Issue
5
Year of publication
1996
Pages
291 - 298
Database
ISI
SICI code
1386-6346(1996)4:5<291:EOAPAC>2.0.ZU;2-4
Abstract
It is well established that several organic anions such as leukotriene C-4 and S-(2,4-dinitrophenyl)-glutathione are excreted into the bile via an ATP-dependent primary active transporter located on the bile ca nalicular membrane. Although the molecular features of this transporte r still remain to be clarified, this transporter might be a member of the ATP-binding cassette (ABC) transmembrane transporter superfamily w hich has a com mon ABC region. In the present study, a cDNA fragment w as amplified from Sprague-Dawley (SD) rat liver by PCR using degenerat e primers prepared from the conserved sequence in the COOH-terminal AB C region of human multidrug resistance-associated protein (MRP), a pri mary active transporter. The amplified 421 bp fragment exhibited homol ogy with a human MRP and the human MRP-like fragment (yp75al1) with ho mology score of 66.3% and 83.0% at the cDNA level, and 73.3% and 84.7% deduced from the amino acid level, respectively. Northern blot analys is of poly(A)(+) RNA prepared from SD rat liver revealed the presence of similar to 5 kb and 8.5 kb mRNA species which hybridized to this fr agment. In contrast, poly(A)(+) RNA from Eisai hyperbilirubinemic rats (EHBR), whose primary active transporter on the bile canalicular memb rane is hereditarily defective, did not hybridize to this fragment. Th ese results suggest (1) that the impaired expression of this particula r region might be related to the pathogenesis of hyperbilirubinemia in EHBR and (2) that this region might encode part of the primary active transporter on the bile canalicular membrane.