Biomedical Engineering Reference
In-Depth Information
The organic cation transporters (Oct and Octn) are important for the transport of or-
ganic cations from blood into kidney.
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All four mouse Octs have very low expression
before birth (Figure 20.6), and their expression increases gradually to adult levels at
3 weeks of age.
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,
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In rats, the developmental expression of Oct1 and 2 also increase
after birth, with consistent increases observed for the first 4 to 6 weeks of age.
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20.3.3. Renal Uptake from Filtrate (Reabsorption)
There are seven Oatps that are expressed in mouse kidneys.
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Of these, Oatp1a1, 1a4,
and possibly 1a6 transport xenobiotics from the lumen into proximal tubules, thus
facilitating reabsorption. The ontogenic pattern of Oatp1a1 is most unusual (Figure
20.7). The renal expression of Oatp1a1 is very low in young mice. Not until 30 days
of age is there any detectable expression of Oatp1a1 in male mouse kidneys. Between
30 and 45 days of age, a marked increase in Oatp1a1 is observed in male but not in
female mice. Thus, a major gender difference in Oatp1a1 is observed in kidneys of
mice. Oatp1a4 is expressed at similar levels from before birth to adulthood. Oatp1a6
exhibits a relatively linear increase in expression during the first 45 days of life.
Oatp2a1 and 2b1 expression are relatively constant from birth to adulthood. The
renal expression of Oatp3a1 before birth is about one-third of that observed in adult
male mice. Oatp3a1 expression remains relatively constant, but at day 30 it increases
in males, resulting in gender differences in expression.
The development of other renal reabsorption transporters in mice has distinctive
ontogenic patterns (Figure 20.7). The concentrative nucleotide transporter 1 (Cnt1)
has a gradual increase in expression during the first 45 days of life. The peptide
transporter (Pept) 2 is relatively low until it reaches its peak expression on day 15.
Oat2 mRNA in mouse kidneys is less at birth than in adults. Oat2 is expressed at very
low levels in mouse kidneys until 30 days of age. After 30 days of age, Oat2 begins to
increase and reaches adult levels by 40 days of age. Oat5 has low fetal expression in
kidney, with a major increase observed at birth. Oat5 expression is relatively constant
until day 22, when it increases in female mice, resulting in a gender difference in
expression. Urat1, the uric acid transporter,
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is expressed at low levels in kidneys
before birth, and gradually increases over the first 6 weeks of age. A male-predominant
gender difference is observed in adult mice.
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The apical sodium bile acid transporter
(Asbt) is expressed at very low levels in the kidney until 3 weeks of age, and by
6 weeks of age it is more highly expressed in female mice.
20.3.4. Renal Efflux into Filtrate
The multidrug resistance-associated protein (Mrp) family of transporters are ex-
tremely important in the efflux of chemicals from cells. In kidney, as in liver, Mrp2
plays a major role in the efflux of chemicals across the apical membrane, and thus
from proximal tubule cells into the filtrate. In mice, Mrp2 expression is very low
before birth and throughout the first 10 days of life, thereafter increasing to adult lev-
els by 15 days of age
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(Figure 20.8). Mrp4 expression gradually increases in kidney
over the first 6 weeks of life.
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