Tissue Distribution, Ontogeny, and Hormonal Regulation of Xenobiotic Transporters in Mouse Kidneys (original) (raw)
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Drug Metabolism and Disposition November 2009, 37 (11) 2178-2185; DOI: https://doi.org/10.1124/dmd.109.027177
Abstract
Kidneys play important roles in the elimination of numerous endogenous and exogenous chemicals. In recent years, at least 37 xenobiotic transporters have been identified in mammalian kidneys. Although much progress has been made, information on 14 of these transporters (ATP-binding cassette [Abc] a1, apical sodium bile acid transporter [Asbt], breast cancer resistance protein, concentrative nucleoside transporter 1, equilibrative nucleoside transporter [Ent] 2, Ent3, sodium-phosphate cotransporter [Npt] 1, Npt2a, Npt2b, Npt2c, organic anion transporter [Oat] 5, organic anion-transporting polypeptide [Oatp] 4c1, peptide transporter 2, and uric acid transporter [Urat] 1) in kidneys is quite limited. Therefore, the purpose of the present study was to examine the tissue distribution, ontogeny, and hormonal regulation of these 14 transporters in kidneys of mice. Other than in kidneys, Npt2b is also highly expressed in liver and lung, Npt2c in liver and colon, Asbt in ileum, and Abca1 in liver, lung, testis, ovary, and placenta of mice. Most of these (13 of 14) transporters are lowly expressed in mouse kidneys until 15 days of age, which in part contributes to the immaturity of excretory function in fetal and newborn kidneys. One exception is Ent2, which is highly expressed before birth and gradually decreases after birth until reaching adult levels at 15 days of age. Gender-divergent expression of male-predominant (Urat1 and Oatp4c1) and female-predominant (Oat5) transporters in mouse kidneys is primarily due to stimulatory effects of androgens and estrogens, respectively. In conclusion, the mRNA expression of xenobiotic transporters in kidneys is determined by tissue, age, and sex hormones.
- Oat, organic anion transporter
- Oct, organic cation transporter
- Oatp, organic anion transporting polypeptide
- Mrp, multidrug resistance-associated protein
- Bcrp, breast cancer resistance protein
- Asbt, apical sodium bile-acid transporter
- Cnt, concentrative nucleoside transporter
- Npt, sodium-phosphate cotransporter
- Urat1, uric acid transporter 1
- Pept, peptide transporter
- Abca1, ATP-binding cassette (Abc) transporter a1
- Ent, equilibrative nucleoside transporter
- Ost, organic solute transporter
- MOPS, 4-morpholinepropanesulfonic acid
- DHT, 5α-dihydroxytestosterone
- E2, estrogen
- GH, growth hormone
- lit/lit, mutation in growth hormone-releasing-hormone receptor gene
- TEA, tetraethylammonium
- bDNA, branched DNA signal amplification assay
- WT, wild-type.
Footnotes
This work was supported by the National Institutes of Health National Institute of Environmental Health Sciences [Grants ES09649, ES09716, ES013714]; and the National Institutes of Health National Center for Research Resources [Grant RR021940].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.109.027177- Received February 16, 2009.
- Accepted August 12, 2009.
Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics
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