Biomedical Engineering Reference
In-Depth Information
LIVER UPTAKE
Ref
17
−
20 5 0 5 3 0 540
45
RLU
220
Oatp1a1
140
17
Oatp1a4
17
22
Oatp1a6
630
17
Oatp1b2
30
17
Oatp2a1
17
85
Oatp2b1
55
np
Ent1
np
470
Ntcp
270
np
Oat2
−
20 5 0 5 2 0 5
200
25
Oct1
FIGURE 20.2.
Ontogenic expression of uptake transporters Oatp1a1, 1a4, 1a6, 1b2, 2a1, and
2b1, Ent1, Ntcp, Oat2, and Oct1 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. np, not published.
Sodium taurocholate cotransporting polypeptide (Ntcp) is a bile acid-uptake
transporter
26
whose ontogenic expression in mice is quite unusual. Ntcp expression
is very low 2 days before birth, attains maximal levels at birth, and then decreases by
5 days of age to fetal levels, remaining low until 23 days of age, when a second sharp
increase in its expression occurs. The Ntcp mRNA gradually decreases afterward, and
then increases in females but not in males at 45 days of age, when the gender differ-
ence in Ntcp mRNA expression becomes apparent. In rats, Ntcp expression appears
to reach adult levels by 1 week of age.
27
20.2.3. Hepatic Efflux into Bile
Many drugs and xenobiotics are metabolized in liver to more water-soluble chem-
icals. Therefore, these metabolites do not readily pass membranes; most chemicals
exit the liver via transporters. Glutathione conjugates are often transported into bile,
and sulfate conjugates are usually transported back into blood, whereas glucuronide
conjugates are transported from the liver into both bile and blood.
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