Human equilibrative nucleoside transporter (ENT) family of nucleoside and nucleobase transporter proteins

New insights regarding the regulation of chemotaxis by nucleotides, adenosine, and their receptors

“…These include an interaction of nucleotides with one or more P2X (ion channel; [15]) and P2Y (G-protein-coupled; [16]) receptors and the enzymatic hydrolysis of ATP (e.g., via the sequential actions of NTPDases and CD73/ecto-5′-nucleotidase; [17]) to generate adenosine. Extracellular adenosine, in turn, can interact with one or more G-protein-coupled P1 receptors [18] or can be taken back up into cells via ENT (equilibrative nucleoside transporter [19]) to undergo metabolic fates that include the synthesis of ATP. One consequence of the activation of P1 (and certain P2Y) receptors is a change in cellular levels of cAMP, which can exit cells by certain multidrug resistant proteins (MRPs 4 and 5; [20]).…”

Identification of the Intracellular Gate for a Member of the Equilibrative Nucleoside Transporter (ENT) Family

“…Clinically, nucleoside and nucleobase analogs are also widely used in anticancer, antiviral, and anti-protozoal therapies (1,2). Because physiological nucleosides and the majority of their synthetic analogs are hydrophilic molecules, specialized nucleoside transporter proteins are required to facilitate their movement across biological membranes.…”

“…Because physiological nucleosides and the majority of their synthetic analogs are hydrophilic molecules, specialized nucleoside transporter proteins are required to facilitate their movement across biological membranes. Thus, nucleoside transporters play key roles in nucleoside physiology, pathophysiology, and in the therapeutic actions of many nucleoside drugs (1)(2)(3)(4)(5).…”

“…The solute carrier 29 (SLC29) 2 (4) family, referred to as equilibrative nucleoside transporters (ENTs), is an important class of permeases that enable facilitated diffusion of nucleosides, nucleobases, and nucleoside analogs into a wide range of eukaryotes (2)(3)(4), although some protozoan members are active proton-coupled symporters that harness energy from the electrochemical gradient across the plasma membrane to concentrate their substrates within the cell (6 -8). Purine nucleoside and nucleobase transporters are of particular interest in parasitic protozoa such as Leishmania, Trypanosoma, and Plasmodium, as none of these organisms is able to synthesize purines de novo, and they are completely reliant upon uptake of preformed purines from their hosts via SLC29 permeases (9).…”

Regulation of bone and cartilage by adenosine signaling

“…There are four known nucleoside transport proteins in human cells (hENT1-4) that facilitate cellular uptake of nucleosides from the surroundings [36]. In both humans and mice, equilibrative nucleoside transporter 1 (ENT1) is widely expressed and responsible for the majority of adenosine transport across the plasma membrane [36]. Knockout mice lacking ENT1 display reduced adenosine uptake and increased circulating levels of adenosine in the plasma [37,38].…”