Nucleoside transporters and liver cell growth

Liver parenchymal cells show a wide variety of plasma membrane transporters that are tightly regulated by endocrine and nutritional factors. This revi ew summarizes work performed in our laboratory on these transport systems, particularly nucleoside transporters, which are up-regulated in physiologic al situations associated with liver cell growth. Rat hepatocytes show a Na-dependent nucleoside transport activity that is stimulated by pancreatic h ormones. Indeed, this biological activity appears to be the result of the c o-expression of at least two isoforms of nucleoside carriers, CNT1 and CNT2 (also called SPNT). These two transporters are up-regulated during the ear ly phase of liver growth after partial hepatectomy, although to different e xtents, suggesting differential regulation of the two isoforms. The recent generation of isoform-specific antibodies allowed us to demonstrate that ca rrier expression may also have complex post-transcriptional regulation on t he basis of the lack of correspondence between mRNA and protein levels. The analysis of nucleoside transport systems in hepatoma cells and the compari son with those in hepatocytes has also provided evidence that the different iation status of liver parenchymal cells may determine the pattern of nucle oside transporters expressed.