The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Correlation of Gene Expression of Ten Drug Efflux Proteins of the ATP-Binding Cassette Transporter Family in Normal Human Jejunum and in Human Intestinal Epithelial Caco-2 Cell Monolayers
Abstract
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 approximately MRP2 > MDR1 approximately MRP3 approximately MRP6 approximately MRP5 approximately 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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Cites
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Cited by
Impact of Drug Transporter Studies on Drug Discovery and Development
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Self-citationGlucagon-Like Peptide-1 Is Involved in Sodium and Water Homeostasis in Humans
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Metadata
- Authors
- Taipalensuu, J., Törnblom, H., Lindberg, G., Einarsson, C., Sjöqvist, F., Melhus, H., Garberg, P., Sjöström, B., Lundgren, B., & Artursson, P.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 299
- Issue
- 1
- Pages
- 164-170
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1943747111
- Cited by
- 444
- References
- 39
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- closed
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- Taipalensuu, J., Törnblom, H., Lindberg, G., Einarsson, C., Sjöqvist, F., Melhus, H., Garberg, P., Sjöström, B., Lundgren, B., & Artursson, P. (2001). Correlation of Gene Expression of Ten Drug Efflux Proteins of the ATP-Binding Cassette Transporter Family in Normal Human Jejunum and in Human Intestinal Epithelial Caco-2 Cell Monolayers. The Journal of Pharmacology and Experimental Therapeutics. https://doi.org/10.1016/s0022-3565(24)29314-9
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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