Tissue distribution, ontogeny, and hormonal regulation of xenobiotic transporters in mouse kidneys

Drug Metab Dispos. 2009 Nov;37(11):2178-85. doi: 10.1124/dmd.109.027177. Epub 2009 Aug 13.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Animals
  • Base Sequence
  • Female
  • Gonadal Steroid Hormones / physiology*
  • Kidney / metabolism*
  • Male
  • Membrane Transport Proteins / biosynthesis
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Organic Anion Transporters / biosynthesis
  • Organic Anion Transporters / genetics
  • Organic Cation Transport Proteins / biosynthesis
  • Organic Cation Transport Proteins / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Tissue Distribution / physiology
  • Xenobiotics / metabolism*

Substances

  • Gonadal Steroid Hormones
  • Membrane Transport Proteins
  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • RNA, Messenger
  • SLC22A10 protein, human
  • SLC22A12 protein, human
  • SLCO4C1 protein, human
  • Xenobiotics