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

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.