SLC29 family members are composed of 11 TM segments with cytoplasmic N-termini and extracellular C-termini. ENT1, ENT2 and ENT4 are primarily cell-surface transporters, while ENT3 is intracellular, possibly lysosomal [2]]. ENT2 isoforms may also play a role in the nucleolar transport of nucleosides [10]. ENT1-3 are described as broad-spectrum equilibrative nucleoside transporters. ENT4 is primarily a polyspecific organic cation transporter at neutral pH [13], but transports adenosine and analogues such as 2-chloroadenosine, with affinities similar to other members of the SLC29 family, at acidic pH [18].

* Key recommended reading is highlighted with an asterisk

* Boswell-Casteel RC, Hays FA. (2017) Equilibrative nucleoside transporters-A review. Nucleosides Nucleotides Nucleic Acids, 36 (1): 7-30. [PMID:27759477]

* Pastor-Anglada M, Pérez-Torras S. (2018) Who Is Who in Adenosine Transport. Front Pharmacol, 9: 627. [PMID:29962948]

* 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]

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. Cerveny L, Ptackova Z, Ceckova M, Karahoda R, Karbanova S, Jiraskova L, Greenwood SL, Glazier JD, Staud F. (2018) Equilibrative Nucleoside Transporter 1 (ENT1, SLC29A1) Facilitates Transfer of the Antiretroviral Drug Abacavir across the Placenta. Drug Metab Dispos, 46 (11): 1817-1826. [PMID:30097436]

5. 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]

6. 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]

7. Deligny M, Crosginani S, Houthuys EJK. (2023) Macrocyclic diamine derivatives as ent inhibitors for the treatment of cancers, and combination thereof with adenosine receptor antagonists. Patent number: US20230203058A1. Assignee: Iteos Therapeutics SA, Iteos Belgium SA. Priority date: 07/04/2021. Publication date: 29/06/2023.

8. 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]

9. Grañe-Boladeras N, Williams D, Tarmakova Z, Stevanovic K, Villani LA, Mehrabi P, Siu KWM, Pastor-Anglada M, Coe IR. (2019) Oligomerization of equilibrative nucleoside transporters: a novel regulatory and functional mechanism involving PKC and PP1. FASEB J, 33 (3): 3841-3850. [PMID:30521377]

10. Grañé-Boladeras N, Spring CM, Hanna WJ, Pastor-Anglada M, Coe IR. (2016) Novel nuclear hENT2 isoforms regulate cell cycle progression via controlling nucleoside transport and nuclear reservoir. Cell Mol Life Sci, 73 (23): 4559-4575. [PMID:27271752]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. Mimura Y, Yasujima T, Ohta K, Inoue K, Yuasa H. (2017) Functional Identification of Plasma Membrane Monoamine Transporter (PMAT/SLC29A4) as an Atenolol Transporter Sensitive to Flavonoids Contained in Apple Juice. J Pharm Sci, 106 (9): 2592-2598. [PMID:28089688]

17. 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]

18. Tandio D, Vilas G, Hammond JR. (2019) Bidirectional transport of 2-chloroadenosine by equilibrative nucleoside transporter 4 (hENT4): Evidence for allosteric kinetics at acidic pH. Sci Rep, 9 (1): 13555. [PMID:31537831]

19. 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]

20. 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]

21. 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]

22. Wright NJ, Lee SY. (2019) Structures of human ENT1 in complex with adenosine reuptake inhibitors. Nat Struct Mol Biol, 26 (7): 599-606. [PMID:31235912]

23. 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]

24. Zhou M, Duan H, Engel K, Xia L, Wang J. (2010) Adenosine transport by plasma membrane monoamine transporter: reinvestigation and comparison with organic cations. Drug Metab Dispos, 38 (10): 1798-805. [PMID:20592246]

25. 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]

Subcommittee members: James R. Hammond (Chairperson) Department of Pharmacology 970 Medical Sciences Bldg University of Alberta Edmonton, AB