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Vol. 299, Issue 1, 164-170, October 2001
Department of Pharmacy, Uppsala University (J.T., P.A.), Department
of Molecular Medicine and Clinical Pharmacology, Uppsala University
Hospital (H.M.), Uppsala, Sweden; Division of Gastroenterology and
Hepatology (H.T., G.L., C.E.) and Clinical Pharmacology (F.S.),
Huddinge University Hospital, Stockholm, Sweden; and Department of In
Vitro Sciences, Pharmacia (P.G., B.S., B.L.), Stockholm, Sweden
This investigation describes the expression and interindividual
variability in transcript levels of multiple drug efflux systems in the
human jejunum and compares the expression profiles in these cells with
that of the commonly used Caco-2 cell drug absorption model. Transcript
levels of ten-drug efflux proteins of the ATP-binding cassette
(ABC) transporter family [MDR1, MDR3, ABCB5, MRP1-6, and
breast cancer resistance protein (BCRP)], lung resistance-related protein (LRP), and CYP3A4 were determined using quantitative polymerase chain reaction in jejunal biopsies from 13 healthy human subjects and
in Caco-2 cells. All genes except ABCB5 were expressed,
and transcript levels varied between individuals only by a factor of 2 to 3. Surprisingly, BCRP and MRP2
transcripts were more abundant in jejunum than MDR1
transcripts. Jejunal transcript levels of the different ABC
transporters spanned a range of three log units with the rank order:
BCRP 
MRP2 > MDR1 MRP3 MRP6 MRP5 MRP1 > MRP4 > MDR3. Furthermore, transcript
levels of 9 of 10 ABC transporters correlated well between jejunum and
Caco-2 cells (r2 = 0.90). However,
BCRP exhibited a 100-fold lower transcript level in
Caco-2 cells compared with jejunum. Thus, the expression of a number of
efflux protein transcripts in jejunum are equal to, or even higher
than, that of MDR1, suggesting that the roles of these
proteins (in particular BCRP and MRP2) in intestinal drug efflux have
been underestimated. Also, we tentatively conclude that the Caco-2 cell
line is a useful model of jejunal drug efflux, if the low expression of
BCRP is taken into account.
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