MULTIDRUG RESISTANCE PROTEINS OF THE ABCC SUBFAMILY - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 282

Apical
membrane
Tight
junction

ABC
C2

ABC
C11

Basolateral
membrane

ABC
C1

ABC
C3

ABC
C4

ABC
C5

ABC
C6

(a)

Human liver

ABCC2 ABCC3

ABCC2 ABCC4 ABCC2 ABCC6

(b)

MDCK- OATP2B1 / ABCC2
Nuclei

MDCK-OATP2B1/ ABCC2
Nuclei

xz plane xz plane

Human liver ABCC2

OATP2B1

ABC
C2

OATP1B1
OATP1B3
OATP2B1

OATP

(c)

FIGURE 11.2. Subcellular localization of ABCC/MRP efflux pumps. ( a ) Schematic rep-
resentation of polarized Madin-Darby canine kidney (MDCK) cells recombinantly express-
ing human ABCC/MRP efflux pumps, which acquire a domain-specific localization either in
the apical membrane (ABCC2, ABCC11) or in the basolateral membrane (ABCC3, ABCC4,
ABCC5, ABCC6). ( b ) Confocal laser scanning micrographs of ABCC/MRP efflux pumps
in human hepatocytes. At least four different ABCC/MRP transporters have been identified
in human hepatocytes [i.e., ABCC2 (red) in the canalicular (apical) membrane and ABCC3,
ABCC4, and ABCC6 (green) in the sinusoidal (basolateral) membrane]. Bars, 20 μ m. ( c )
Confocal laser scanning micrographs of MDCK cells simultaneously expressing recombinant
human OATP2B1 (green) as an uptake transporter and ABCC2 (red) as an efflux pump for
organic anions. The lines indicate where the optical xz-sections had been taken. These double-
transfected cells serve as valuable tools to study the vectorial transport of organic anions that
undergo hepatobiliary elimination. In human hepatocytes, OATP2B1 (green) is located in the
sinusoidal membrane and ABCC2 (red) in the canalicular membrane. Bars, 10 μ m. ( See insert
for color representation of figure .)