Biomedical Engineering Reference
In-Depth Information
LIVER EFFLUX INTO BILE
−
-2
20 5 0 5 3 0 540
0
5
10
15
23
30
35
40
45
45
RLU
RLU
480
Ref
30
RLU
Mrp2
Mrp2
Mate1
225
np
Bcrp
Mate2
32
np
Bsep
Mdr1b
22
np
Mdr1b
Mdr2
219
np
Mdr2
Bcrp
np
130
Bcrp
Bsep
300
np
Bsep
AbcG5
100
np
AbcG5
AbcG8
np
85
AbcG8
FIGURE 20.3.
Ontogenic expression of canalicular (apical) efflux transporters Abcg5 and
g8, Bcrp, Bsep, Mate1, Mate2, Mdr1b, Mdr2, and Mrp2 in livers of male and female mice.
The total RNA from C57BL/6 mice at each age (
n
=
5/gender) was analyzed by the bDNA
method. Data are presented as a ratio of mRNA expression at that age to the highest observed
in mouse liver. RLU (relative light unit) represents the highest mRNA expression observed in
mouse liver.
represents mRNA expression levels in male mouse liver;
represents mRNA
expression levels in female mouse liver.
The multidrug resistance-associated protein (Mrp) family has the major role of
transporting chemicals out of cells.
28
Mrp2 is highly expressed in liver and is re-
sponsible for hepatobiliary excretion of reduced and oxidized glutathione as well
as glutathione and glucuronide conjugates. Hepatobiliary disposition of conjugated
bilirubin is impaired in Dubin-Johnson syndrome patients, who have nonfunctional
Mrp2.
29
As noted in Figure 20.3, the mRNA expression of Mrp2 in livers is very low
in mice before birth. At birth, Mrp2 reaches its highest expression.
30
In rats, there is
also no marked increase in Mrp2 mRNA between 1 day of age and maturity.
31
,
32
The multidrug and toxin extrusion (Mate) family consists of two transporters, and
both are localized in the bile canaliculus and excrete cationic drugs.
33
,
34
As noted in
Figure 20.3, the expression of Mate1 and of Mate2 were relatively the same at all
ages except for a “surge” at birth.
The multidrug resistance protein (Mdr) family of transporters also transport chemi-
cals across the canaliculus into bile. Whereas neither Mdr1a nor 1b is highly expressed
in liver, Mdr1b appears to be more abundant than Mdr1a in the liver of mice. These
transporters often transport bulky neutral and cationic chemicals.
35
As noted in Figure
20.3, Mdr1b is expressed similarly in mice of all ages, and no gender differences are
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