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

Abstract

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 K m 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 T 3 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.