Biomedical Engineering Reference
In-Depth Information
RENAL EFFLUX INTO FILTRATE
2
0
5 0 5 2 0 5RLU
60
Ref
30
−
Mrp2
21
30
Mrp4
108
np
Mdr1b
Bcrp
930
np
FIGURE 20.8.
Ontogenic expression of apical efflux transporters Bcrp, Mdr1b, Mrp2, and
Mrp4 in proximal tubular cells (PTCs) of kidneys 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 kidney.
RLU (relative light unit) represents the highest mRNA expression observed in mouse kidney.
represents mRNA expression levels in male mouse kidney;
represents mRNA expression
levels in female mouse kidney.
10 to 22, Mdr1b expression increases, whereas expression decreases between days
30 and 45 in male mice, resulting in a gender difference in expression of Mdr1b.
The equilibrative nucleoside transporter (Ent) 2 and 3 are expressed in kidney.
22
Ent2 is expressed similarly at various ages in mouse kidneys, whereas Ent3 shows a
continuous increase in expression from birth through day 45.
20.3.5. Renal Efflux into Blood
The Mrps in kidneys, not only efflux chemicals into the filtrate but can also transport
xenobiotics into blood (Figures 20.5 and 20.9). Whereas Mrp2 and 4 are localized
in the apical portion of renal tubular cell, Mrp1, 3, 5, and 6 exist in the basolateral
portion of renal tubular cell membranes and efflux chemicals back into blood.
59
,
60
Figure 20.9 illustrates the developmental pattern of expression of these four Mrps.
Mrp1 expression is relatively constant at various ages in mice
30
and rats;
31
however,
its expression is higher at days 0 and 15 than at other ages. A later decrease in
expression in male mouse kidneys results in a female-predominant gender difference.
Mrp3 expression in kidney is low until 15 days of age, when the expression triples.
30
At 30 days of age, Mrp3 expression in male kidneys decreases, also resulting in a
female-predominant gender difference in expression. Mrp5 expression in kidney is
similar before birth as in adult mice, but its expression is at least twice as high at
birth, but then it gradually decreases to adult expression levels. Mrp6 is expressed at
high levels before birth and gradually increases to levels observed in adults.
Organic solute transporters (Ost)
are important for effluxing bile acids
from enterocytes back into blood.
61
In kidneys, they also probably transfer chemicals
back into blood.
44
and
both have low expression before birth, increase to
about one-fourth of adult expression at birth, and reach maturity between 10 and 15
days of age (Figure 20.9).
Ost
and
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