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)
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
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.