ENT Tissue Distribution and Regulation

In summary, ENTl can actually be a major player in the regulation of extracellular adenosine levels in different cell types, particularly in those such as HUVEC, in which no CNT proteins appear to be coexpressed. From this viewpoint, it is a suitable pharmacological target in the treatment of cardiovascular diseases. 

Nevertheless, ENTl also seems to fulfill nucleoside salvage requirements. It is a broad selectivity, ubiquitous plasma membrane transporter that, in turn, seems to be regulated by proliferative stimuli. In murine bone marrow macrophages, ENTl is upregulated by M-CSF, thus promoting the incorporation of extracellular nucleosides into DNA (but not into RNA), a process that, when blocked by NBTI, results in the inhibition of cell proliferation [43]. When macrophages are treated with 

As previously discussed, it is now well accepted that CNTs show broad tissue distribution, although it is also true that some cell types lack either any CNT or particular CNT isoform expression. Moreover, it is also common that their function-related activity gets lost easily in primary culture preparations, whereas commercially available cell lines may also lack CNT-related activities. Overall, this makes it difficult to work with, and the identification and/or generation of suitable cell models is a major bottleneck in the field. 

In summary, CNTs in epithelia might be major players in determining vectorial flux of nucleosides, thus contributing to absorption and reabsorption phenomena and, consequently, to whole-body nucleoside homeostasis. 

Hepatocyte models are now available to further study the role of CNT proteins in liver physiology. They have also provided the first evidence of regulated intracellular transporter trafficking being used to dissect these phenomena at the molecular level. 

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