PMID- 10094960
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20171213
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 29
IP  - 4
DP  - 1999 Apr
TI  - Characterization of the human multidrug resistance protein isoform MRP3 localized
      to the basolateral hepatocyte membrane.
PG  - 1156-63
AB  - Several members of the multidrug resistance protein (MRP) family are expressed in
      the liver. Adenosine triphosphate (ATP)-dependent transport of glutathione and
      glucuronoside conjugates across the hepatocyte canalicular membrane is mediated
      by the apical MRP isoform, MRP2 (APMRP), also known as canalicular multispecific 
      organic anion transporter (cMOAT). We have cloned an additional MRP isoform,
      MRP3, from human liver and localized it to the basolateral membrane domain of
      hepatocytes. Basolateral MRP (BLMRP) is composed of 1,527 amino acids and encoded
      by 4,581 base pairs of complementary DNA. Northern blotting of various human
      tissues indicated an expression of MRP3 in the liver, colon, pancreas, and, at a 
      lower level, in the kidney. The amino acid identity of MRP3 with MRP1 and MRP2 is
      58% and 48%, respectively. These three isoforms, encoded by genes on different
      chromosomes, have a similar predicted topology of transmembrane segments and
      ATP-binding domains. Antibodies raised against two peptide sequences of MRP3 that
      are not shared by other MRP family members detected recombinant MRP3 expressed in
      polarized MDCK cells. Both antibodies served to localize MRP3 to the basolateral 
      membrane of hepatocytes. Double-label immunofluorescence microscopy confirmed
      that MRP3 was not detectable in the canalicular membrane domain. A particularly
      strong expression of the MRP3 protein was observed in the basolateral hepatocyte 
      membrane of two patients with Dubin-Johnson syndrome who are deficient in MRP2.
      These results indicate that the basolateral MRP isoform, MRP3, may be upregulated
      when the canalicular secretion of anionic conjugates by MRP2 is impaired.
FAU - Konig, J
AU  - Konig J
AD  - Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg,
      Germany. j.koenig@dkfz-heidelberg.de
FAU - Rost, D
AU  - Rost D
FAU - Cui, Y
AU  - Cui Y
FAU - Keppler, D
AU  - Keppler D
LA  - eng
SI  - GENBANK/Y17151
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 1YV0492L5Z (multidrug resistance-associated protein 3)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*genetics/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cloning, Molecular
MH  - Dogs
MH  - Drug Resistance, Multiple/*genetics
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoblotting
MH  - Liver/*metabolism
MH  - Molecular Sequence Data
MH  - *Multidrug Resistance-Associated Proteins
MH  - Organ Specificity
MH  - Sequence Alignment
EDAT- 1999/03/30 00:00
MHDA- 1999/03/30 00:01
CRDT- 1999/03/30 00:00
PHST- 1999/03/30 00:00 [pubmed]
PHST- 1999/03/30 00:01 [medline]
PHST- 1999/03/30 00:00 [entrez]
AID - S0270913999001780 [pii]
AID - 10.1002/hep.510290404 [doi]
PST - ppublish
SO  - Hepatology. 1999 Apr;29(4):1156-63. doi: 10.1002/hep.510290404.