ENT2

ENT2 (equilibrative nucleoside transporter 2) is a membrane transporter protein belonging to the equilibrative nucleoside transporter (ENT) family. It mediates the facilitated diffusion of nucleosides across the cell membrane down their concentration gradients and is encoded in humans by the SLC29A2 gene.

Substrate range and function: ENT2 transports a range of nucleosides, including adenosine, inosine, guanosine, cytidine, and thymidine, as well as several nucleoside analogs used in chemotherapy and antiviral therapy. It works together with other ENTs (notably ENT1) to regulate cellular nucleoside availability and intracellular adenosine signaling. Compared with ENT1, ENT2 generally exhibits lower affinity but higher capacity, and its contribution is particularly important in tissues where ENT1 activity is limited or inhibited.

Expression and role: ENT2 is widely expressed in many tissues and contributes to nucleoside salvage pathways, influencing purinergic signaling and energy metabolism by modulating intracellular adenosine concentration. It also participates in uptake of nucleoside-based drugs, affecting pharmacokinetics and pharmacodynamics.

Clinical and pharmacological relevance: Variation in SLC29A2 or ENT2 activity can affect responses to nucleoside drugs, including antivirals and anticancer agents, and may influence drug toxicity profiles. ENT2 inhibitors or modulators are used in research to study nucleoside transport and to optimize drug delivery.

Regulation and inhibitors: ENTs can be inhibited by nucleoside transport inhibitors such as nitrobenzylthioinosine (NBMPR) and dipyridamole or dilazep in experimental settings, and transporter activity can be influenced by cellular energy status and extracellular nucleotide concentrations. ENT2 thus plays a role in both normal nucleoside homeostasis and the pharmacology of nucleoside-based therapies.