Tissue distribution, ontogeny, and hormonal regulation of xenobiotic transporters in mouse kidneys.
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.
Cheng
Xingguo
X
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
Klaassen
Curtis D
CD
D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014018:Tissue Distribution / Q000502:physiology; D015262:Xenobiotics / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C427208:SLC22A10 protein, human; C491241:SLC22A12 protein, human; C484530:SLCO4C1 protein, human; D015262:Xenobiotics
Drug Metab Dispos. 2005 Jul;33(7):1062-73
15843488
Biochem Pharmacol. 2006 May 14;71(10):1470-8
16529719
J Biol Chem. 2002 May 31;277(22):19665-72
11880379
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74
14993604
Am J Physiol. 1998 Oct;275(4):F527-34
9755124
Mol Endocrinol. 1990 Dec;4(12):1943-55
1707128
Cell. 1989 Feb 10;56(3):335-44
2644044
J Clin Invest. 1971 Apr;50(4):779-95
5547275
Drug Metab Dispos. 2004 Dec;32(12):1455-61
15371301
Endocrinology. 1994 Jan;134(1):432-40
8275956
Drug Metab Dispos. 2006 Nov;34(11):1863-7
16928788
Am J Physiol. 1970 Oct;219(4):1061-5
5459469
Am J Physiol. 1961 Oct;201:743-6
14491491
J Pharmacol Exp Ther. 1998 Sep;286(3):1391-6
9732402
Drug Metab Dispos. 2000 May;28(5):608-16
10772642
Peptides. 2006 Apr;27(4):850-7
16202478
Nature. 2002 May 23;417(6887):447-52
12024214
Drug Metab Dispos. 2005 Jul;33(7):947-55
15802388
Biochem Biophys Res Commun. 2005 Jan 7;326(1):181-7
15567169
J Am Soc Nephrol. 2004 Feb;15(2):261-8
14747372
Mol Pharmacol. 2006 Oct;70(4):1291-7
16807376
Drug Metab Dispos. 2006 Mar;34(3):477-82
16381671
Biol Neonate. 1976;28(1-2):57-64
2340
Drug Metab Dispos. 2004 Jun;32(6):620-5
15155553
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14564-9
9826740
J Clin Invest. 1963 Oct;42:1632-9
14074357