Developmental regulation of the concentrative nucleoside transporters CNT1 and CNT2 in rat liver

J Hepatol. 2001 Jun;34(6):873-80. doi: 10.1016/s0168-8278(01)00036-8.


Background/aims: The pattern of nucleoside transporter expression in hepatocytes was studied in the developing rat liver.

Methods: Hepatocytes isolated from fetuses, neonates and adult rats were used for uridine uptake measurements and concentrative nucleoside transporter (CNT) expression.

Results: Adult hepatocytes showed the highest Na-dependent uridine uptake, but fetal hepatocytes exhibited a significant NBTI-sensitive component of equilibrative Na+-independent transport, which was either negligible or absent in neonatal and adult rat hepatocytes. Low Na+-dependent uridine uptake was associated with low amounts of CNT1 and CNT2 transporter proteins, both with apparent Km values in the low micromolar range. Hepatocyte primary cultures from 20-day-old fetuses showed very low amounts of CNT2 mRNA, and expressed both carrier proteins. Incubation of fetal hepatocytes with dexamethasone and T3 resulted in a significant increase in Na+-dependent uridine uptake and an accumulation of the CNT2 protein and mRNA.

Conclusions: The expression of concentrative nucleoside carriers in hepatocytes from developing rat liver is developmentally regulated. Addition of endocrine factors known to induce differentiation of fetal hepatocytes results in selective up-regulation of CNT2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Transport, Active / drug effects
  • Cell Differentiation / drug effects
  • Dexamethasone / pharmacology
  • Embryonic and Fetal Development
  • Female
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • In Vitro Techniques
  • Liver / drug effects
  • Liver / embryology
  • Liver / growth & development*
  • Liver / metabolism*
  • Membrane Transport Modulators
  • Membrane Transport Proteins / antagonists & inhibitors
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Thioinosine / analogs & derivatives*
  • Thioinosine / pharmacology
  • Triiodothyronine / pharmacology
  • Uridine / metabolism


  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • RNA, Messenger
  • cif nucleoside transporter
  • Triiodothyronine
  • Thioinosine
  • Dexamethasone
  • 4-nitrobenzylthioinosine
  • Uridine