ENT1

ENT1, short for equilibrative nucleoside transporter 1, is a member of the solute carrier SLC29 family. It is a bidirectional, sodium-independent membrane transporter that enables facilitated diffusion of nucleosides across the plasma membrane, driven by the cell’s nucleoside concentration gradients. The protein is an integral membrane protein with multiple transmembrane domains.

Substrates transported by ENT1 include a range of purine and pyrimidine nucleosides such as adenosine, inosine, guanosine, cytidine, and thymidine. By enabling cellular uptake and release of nucleosides, ENT1 participates in nucleotide salvage pathways and helps regulate extracellular adenosine levels, which can influence adenosine receptor signaling and downstream physiological responses.

Expression of ENT1 is widespread, with notable presence in tissues such as the brain, heart, liver, kidney, and immune cells, as well as erythrocytes. In pharmacology, ENT1 is important for the cellular uptake of nucleoside analog drugs, including cytarabine (Ara-C), gemcitabine, and other antivirals, making it a determinant of drug efficacy in certain settings.

Inhibitors of ENT1 include nitrobenzylthioinosine (NBMPR), a potent and relatively selective blocker of ENT1, while dipyridamole inhibits both ENT1 and ENT2. Regulation of ENT1 activity and expression can affect adenosine availability and responses to nucleoside-based therapies. The SLC29A1 gene encodes ENT1, and genetic variation or altered expression can influence therapeutic outcomes and adenosine metabolism in various clinical contexts.