AGE- AND GENDER-RELATED DIFFERENCES IN XENOBIOTIC TRANSPORTER EXPRESSION - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 605

expressed in the intestine of the fetus, reaches its maximum expression at 2 to 3 weeks
of age, and decreases to an adult level lower than that in the fetus.
The intestinal bile acid transporter, also known as the apical sodium bile acid
transporter (Ibat/Asbt), is expressed at similar levels in all ages examined. In rats, the
Asbt protein is very low before 3 weeks of age. 62 Oatp2b1 mRNA is expressed at a
similar level in enterocytes of mice of all ages. The organic cation transporter (Octn1)
is expressed from 2 days before birth through the first month of life at about one-half
that observed in 45-day-old mice. 25 The peptide transporter (pept) 1 expression is
nonexistent two days before birth, but expression increases gradually over the first
month to adult levels.

20.4.2. Intestinal Efflux into Lumen

The intestinal efflux transporters are important in preventing the absorption of some
chemicals into the systemic circulation. For example, Mdr1a decreases the absorption
of many bulky cationic organic compounds. As noted in Figure 20.12, Mdr1a expres-
sion in the intestine is low 2 days before birth but is expressed at nearly adult levels
at birth, continuing through adulthood. Mrp2 is expressed in mouse intestine before
birth, maximally expressed at days 0 to 15, and decreases by more than 50% to adult
levels. Mrp7 is expressed at constant levels from 2 days before birth to adulthood. 30
Abcg5 and g8 prevent the absorption of plant sterols. 63 , 64 The ontogenic patterns for
Abcg5 and g8 are quite different (Figure 20.12). Abcg5 reaches its maximum expres-
sion at day 15 and then decreases, whereas Abcg8 reaches its maximum expression
earlier (days 5 and 10), and then decreases markedly.

INTESTINAL EFFLUX INTO LUMEN
-2

Ref

− 20 0 5 5 0 5 3 0 5 10 530 5 RLU RLU RLU

np

345 345

Mdr1a

Mdr1a

2900 np

Mrp2

Mrp2

np

180

Mrp7

Mrp7

np

Abcg5 536

AbcG5

390 np

Abcg8

AbcG8

FIGURE 20.12. Ontogenic expression of apical efflux transporters Abcg5 and g8, Mdr1a,
Mrp2, and Mrp7 in enterocytes of male mice. Previous studies showed that there is no gender
difference in mRNA expression of these transporters in the adult mouse duodenum. Therefore,
the total RNA from male C57BL/6 mouse duodenum at each age ( n = 5) was analyzed by

the bDNA method. Data are presented as the ratio of mRNA expression at that age to the
highest observed in mouse duodenum. RLU (relative light unit) represents the highest mRNA
expression observed in mouse duodenum.