SLC29 family members appear to be composed of 11 TM segments with cytoplasmic N-termini and extracellular C-termini. ENT1, ENT2 and ENT4 are cell-surface transporters, while ENT3 is intracellular, possibly lysosomal [2]. ENT1-3 are described as broad-spectrum equilibrative nucleoside transporters, while ENT4 is primarily a polyspecific organic cation transporter at neutral pH [9]. ENT4 transports adenosine only under acidotic conditions [3].

1. Armstrong D, Summers C, Ewart L, Nylander S, Sidaway JE, van Giezen JJ. (2014) Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1. J. Cardiovasc. Pharmacol. Ther., 19 (2): 209-19. [PMID:24414167]

2. Baldwin SA, Yao SY, Hyde RJ, Ng AM, Foppolo S, Barnes K, Ritzel MW, Cass CE, Young JD. (2005) Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J. Biol. Chem., 280 (16): 15880-7. [PMID:15701636]

3. Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, Sun L, Tellez J, Ritzel MW, Claycomb WC et al.. (2006) Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ. Res., 99 (5): 510-9. [PMID:16873718]

4. Choi MK, Kim MH, Maeng HJ, Song IS. (2015) Contribution of CNT1 and ENT1 to ribavirin uptake in human hepatocytes. Arch. Pharm. Res., 38 (5): 904-13. [PMID:25011570]

5. Daniels G, Ballif BA, Helias V, Saison C, Grimsley S, Mannessier L, Hustinx H, Lee E, Cartron JP, Peyrard T et al.. (2015) Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization. Blood, 125 (23): 3651-4. [PMID:25896650]

6. Engel K, Wang J. (2005) Interaction of organic cations with a newly identified plasma membrane monoamine transporter. Mol. Pharmacol., 68 (5): 1397-407. [PMID:16099839]

7. Hammond JR. (2000) Interaction of a series of draflazine analogues with equilibrative nucleoside transporters: species differences and transporter subtype selectivity. Naunyn Schmiedebergs Arch. Pharmacol., 361 (4): 373-82. [PMID:10763851]

8. Hammond JR, Archer RG. (2004) Interaction of the novel adenosine uptake inhibitor 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride (KF24345) with the es and ei subtypes of equilibrative nucleoside transporters. J. Pharmacol. Exp. Ther., 308 (3): 1083-93. [PMID:14634039]

9. Ho HT, Pan Y, Cui Z, Duan H, Swaan PW, Wang J. (2011) Molecular analysis and structure-activity relationship modeling of the substrate/inhibitor interaction site of plasma membrane monoamine transporter. J. Pharmacol. Exp. Ther., 339 (2): 376-85. [PMID:21816955]

10. Hsu CL, Lin W, Seshasayee D, Chen YH, Ding X, Lin Z, Suto E, Huang Z, Lee WP, Park H et al.. (2012) Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis. Science, 335 (6064): 89-92. [PMID:22174130]

11. Kang N, Jun AH, Bhutia YD, Kannan N, Unadkat JD, Govindarajan R. (2010) Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability. J. Biol. Chem., 285 (36): 28343-52. [PMID:20595384]

12. Sundaram M, Yao SY, Ng AM, Griffiths M, Cass CE, Baldwin SA, Young JD. (1998) Chimeric constructs between human and rat equilibrative nucleoside transporters (hENT1 and rENT1) reveal hENT1 structural domains interacting with coronary vasoactive drugs. J. Biol. Chem., 273 (34): 21519-25. [PMID:9705281]

13. Wang C, Lin W, Playa H, Sun S, Cameron K, Buolamwini JK. (2013) Dipyridamole analogs as pharmacological inhibitors of equilibrative nucleoside transporters. Identification of novel potent and selective inhibitors of the adenosine transporter function of human equilibrative nucleoside transporter 4 (hENT4). Biochem. Pharmacol., 86 (11): 1531-40. [PMID:24021350]

14. Wang J. (2016) The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition. Clin. Pharmacol. Ther., 100 (5): 489-499. [PMID:27506881]

15. Warraich S, Bone DB, Quinonez D, Ii H, Choi DS, Holdsworth DW, Drangova M, Dixon SJ, Séguin CA, Hammond JR. (2013) Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans. J. Bone Miner. Res., 28 (5): 1135-49. [PMID:23184610]

16. Yao SY, Ng AM, Cass CE, Baldwin SA, Young JD. (2011) Nucleobase transport by human equilibrative nucleoside transporter 1 (hENT1). J. Biol. Chem., 286 (37): 32552-62. [PMID:21795683]

17. Zhou M, Xia L, Wang J. (2007) Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab. Dispos., 35 (10): 1956-62. [PMID:17600084]

James R. Hammond Department of Pharmacology 970 Medical Sciences Bldg University of Alberta Edmonton, AB