Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [17]. Since the isolation and cloning of the first aquaporin (AQP1) [21], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [5]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [16], and superaquaporins (AQP11 and 12) located within cells [14]. Some aquaporins also conduct ammonia and/or H₂O₂ giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1 [16]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [27]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia and loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [24], Kitchen et al. (2105) [16]].

Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six transmembrane helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [17]. In addition to the four pores contributed by the protomers, an additional hydrophobic pore exists within the center of the complex [17] that may mediate the transport of gases (e.g. O₂, CO₂, NO) and cations (the central pore is the proposed transport pathway for cations through AQP1) by some AQPs [8,15]. Although numerous small molecule inhibitors of aquaporins, particularly APQ1, have been reported primarily from Xenopus oocyte swelling assays, the activity of most has subsequently been disputed upon retesting using assays of water transport that are less prone to various artifacts [6] and they are therefore excluded from the tables [see Tradtrantip et al. (2017) [23] for a review].

* Key recommended reading is highlighted with an asterisk

* Agre P. (2006) The aquaporin water channels. Proc Am Thorac Soc, 3 (1): 5-13. [PMID:16493146]

* Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Nielsen S. (2002) Aquaporin water channels--from atomic structure to clinical medicine. J. Physiol. (Lond.), 542 (Pt 1): 3-16. [PMID:12096044]

Babey M, Kopp P, Robertson GL. (2011) Familial forms of diabetes insipidus: clinical and molecular characteristics. Nat Rev Endocrinol, 7 (12): 701-14. [PMID:21727914]

* Beitz E, Golldack A, Rothert M, von Bülow J. (2015) Challenges and achievements in the therapeutic modulation of aquaporin functionality. Pharmacol. Ther., 155: 22-35. [PMID:26277280]

Bockenhauer D, Bichet DG. (2015) Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol, 11 (10): 576-88. [PMID:26077742]

* Carbrey JM, Agre P. (2009) Discovery of the aquaporins and development of the field. Handb Exp Pharmacol, (190): 3-28. [PMID:19096770]

Castle NA. (2005) Aquaporins as targets for drug discovery. Drug Discov. Today, 10 (7): 485-93. [PMID:15809194]

de Groot BL, Grubmüller H. (2005) The dynamics and energetics of water permeation and proton exclusion in aquaporins. Curr. Opin. Struct. Biol., 15 (2): 176-83. [PMID:15837176]

Frigeri A, Nicchia GP, Svelto M. (2007) Aquaporins as targets for drug discovery. Curr. Pharm. Des., 13 (23): 2421-7. [PMID:17692010]

* Geng X, Yang B. (2017) Transport Characteristics of Aquaporins. Adv. Exp. Med. Biol., 969: 51-62. [PMID:28258565]

* Ishibashi K, Hara S, Kondo S. (2009) Aquaporin water channels in mammals. Clin. Exp. Nephrol., 13 (2): 107-17. [PMID:19085041]

Jeyaseelan K, Sepramaniam S, Armugam A, Wintour EM. (2006) Aquaporins: a promising target for drug development. Expert Opin. Ther. Targets, 10 (6): 889-909. [PMID:17105375]

Kimelberg HK. (2004) Water homeostasis in the brain: basic concepts. Neuroscience, 129 (4): 851-60. [PMID:15561403]

King LS, Kozono D, Agre P. (2004) From structure to disease: the evolving tale of aquaporin biology. Nat. Rev. Mol. Cell Biol., 5 (9): 687-98. [PMID:15340377]

* Kitchen P, Day RE, Salman MM, Conner MT, Bill RM, Conner AC. (2015) Beyond water homeostasis: Diverse functional roles of mammalian aquaporins. Biochim. Biophys. Acta, 1850 (12): 2410-21. [PMID:26365508]

Papadopoulos MC, Verkman AS. (2013) Aquaporin water channels in the nervous system. Nat. Rev. Neurosci., 14 (4): 265-77. [PMID:23481483]

Rojek A, Praetorius J, Frøkiaer J, Nielsen S, Fenton RA. (2008) A current view of the mammalian aquaglyceroporins. Annu. Rev. Physiol., 70: 301-27. [PMID:17961083]

Takeda T, Taguchi D. (2009) Aquaporins as potential drug targets for Meniere's disease and its related diseases. Handb Exp Pharmacol, (190): 171-84. [PMID:19096777]

* Tesse A, Grossini E, Tamma G, Brenner C, Portincasa P, Marinelli RA, Calamita G. (2018) Aquaporins as Targets of Dietary Bioactive Phytocompounds. Front Mol Biosci, 5: 30. [PMID:29721498]

* Tradtrantip L, Jin BJ, Yao X, Anderson MO, Verkman AS. (2017) Aquaporin-Targeted Therapeutics: State-of-the-Field. Adv. Exp. Med. Biol., 969: 239-250. [PMID:28258578]

Verkman AS. (2009) Aquaporins: translating bench research to human disease. J. Exp. Biol., 212 (Pt 11): 1707-15. [PMID:19448080]

Wang F, Feng XC, Li YM, Yang H, Ma TH. (2006) Aquaporins as potential drug targets. Acta Pharmacol. Sin., 27 (4): 395-401. [PMID:16539837]

* Yang B. (2017) Aquaporins. In Advances in Experimental Medicine and Biology Edited by Yang B (Springer) 1-276. [ISBN:9789402410570]

1. Alexander SP, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA et al.. (2015) The Concise Guide to PHARMACOLOGY 2015/16: Other ion channels. Br. J. Pharmacol., 172 (24): 5942-55. [PMID:26650442]

2. Alexander SP, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA et al.. (2017) THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Other ion channels. Br. J. Pharmacol., 174 Suppl 1: S195-S207. [PMID:29055039]

3. Bienert GP, Chaumont F. (2014) Aquaporin-facilitated transmembrane diffusion of hydrogen peroxide. Biochim. Biophys. Acta, 1840 (5): 1596-604. [PMID:24060746]

4. Chow PH, Kourghi M, Pei JV, Nourmohammadi S, Yool AJ. (2020) 5-Hydroxymethyl-Furfural and Structurally Related Compounds Block the Ion Conductance in Human Aquaporin-1 Channels and Slow Cancer Cell Migration and Invasion. Mol. Pharmacol., 98 (1): 38-48. [PMID:32434851]

5. Day RE, Kitchen P, Owen DS, Bland C, Marshall L, Conner AC, Bill RM, Conner MT. (2014) Human aquaporins: regulators of transcellular water flow. Biochim. Biophys. Acta, 1840 (5): 1492-506. [PMID:24090884]

6. Esteva-Font C, Jin BJ, Lee S, Phuan PW, Anderson MO, Verkman AS. (2016) Experimental Evaluation of Proposed Small-Molecule Inhibitors of Water Channel Aquaporin-1. Mol. Pharmacol., 89 (6): 686-93. [PMID:26993802]

7. Garneau AP, Carpentier GA, Marcoux AA, Frenette-Cotton R, Simard CF, Rémus-Borel W, Caron L, Jacob-Wagner M, Noël M, Powell JJ et al.. (2015) Aquaporins Mediate Silicon Transport in Humans. PLoS ONE, 10 (8): e0136149. [PMID:26313002]

8. Geyer RR, Musa-Aziz R, Qin X, Boron WF. (2013) Relative CO(2)/NH(3) selectivities of mammalian aquaporins 0-9. Am. J. Physiol., Cell Physiol., 304 (10): C985-94. [PMID:23485707]

9. Herrera M, Hong NJ, Garvin JL. (2006) Aquaporin-1 transports NO across cell membranes. Hypertension, 48 (1): 157-64. [PMID:16682607]

10. Holm LM, Jahn TP, Møller AL, Schjoerring JK, Ferri D, Klaerke DA, Zeuthen T. (2005) NH3 and NH4+ permeability in aquaporin-expressing Xenopus oocytes. Pflugers Arch., 450 (6): 415-28. [PMID:15988592]

11. Holm LM, Klaerke DA, Zeuthen T. (2004) Aquaporin 6 is permeable to glycerol and urea. Pflugers Arch., 448 (2): 181-6. [PMID:14985982]

12. Ishibashi K, Kuwahara M, Gu Y, Kageyama Y, Tohsaka A, Suzuki F, Marumo F, Sasaki S. (1997) Cloning and functional expression of a new water channel abundantly expressed in the testis permeable to water, glycerol, and urea. J. Biol. Chem., 272 (33): 20782-6. [PMID:9252401]

13. Ishibashi K, Morinaga T, Kuwahara M, Sasaki S, Imai M. (2002) Cloning and identification of a new member of water channel (AQP10) as an aquaglyceroporin. Biochim. Biophys. Acta, 1576 (3): 335-40. [PMID:12084581]

14. Ishibashi K, Tanaka Y, Morishita Y. (2014) The role of mammalian superaquaporins inside the cell. Biochim. Biophys. Acta, 1840 (5): 1507-12. [PMID:24189537]

15. Kaldenhoff R, Kai L, Uehlein N. (2014) Aquaporins and membrane diffusion of CO2 in living organisms. Biochim. Biophys. Acta, 1840 (5): 1592-5. [PMID:24141139]

16. Kitchen P, Day RE, Salman MM, Conner MT, Bill RM, Conner AC. (2015) Beyond water homeostasis: Diverse functional roles of mammalian aquaporins. Biochim. Biophys. Acta, 1850 (12): 2410-21. [PMID:26365508]

17. Kreida S, Törnroth-Horsefield S. (2015) Structural insights into aquaporin selectivity and regulation. Curr. Opin. Struct. Biol., 33: 126-34. [PMID:26342685]

18. Ma T, Yang B, Verkman AS. (1997) Cloning of a novel water and urea-permeable aquaporin from mouse expressed strongly in colon, placenta, liver, and heart. Biochem. Biophys. Res. Commun., 240 (2): 324-8. [PMID:9388476]

19. Madeira A, Fernández-Veledo S, Camps M, Zorzano A, Moura TF, Ceperuelo-Mallafré V, Vendrell J, Soveral G. (2014) Human aquaporin-11 is a water and glycerol channel and localizes in the vicinity of lipid droplets in human adipocytes. Obesity (Silver Spring), 22 (9): 2010-7. [PMID:24845055]

20. Martins AP, Marrone A, Ciancetta A, Galán Cobo A, Echevarría M, Moura TF, Re N, Casini A, Soveral G. (2012) Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound. PLoS ONE, 7 (5): e37435. [PMID:22624030]

21. Preston GM, Carroll TP, Guggino WB, Agre P. (1992) Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science, 256 (5055): 385-7. [PMID:1373524]

22. Rambow J, Wu B, Rönfeldt D, Beitz E. (2014) Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogen-host interactions. Front Pharmacol, 5: 199. [PMID:25225485]

23. Tradtrantip L, Jin BJ, Yao X, Anderson MO, Verkman AS. (2017) Aquaporin-Targeted Therapeutics: State-of-the-Field. Adv. Exp. Med. Biol., 969: 239-250. [PMID:28258578]

24. Verkman AS, Anderson MO, Papadopoulos MC. (2014) Aquaporins: important but elusive drug targets. Nat Rev Drug Discov, 13 (4): 259-77. [PMID:24625825]

25. Wang Y, Tajkhorshid E. (2010) Nitric oxide conduction by the brain aquaporin AQP4. Proteins, 78 (3): 661-70. [PMID:19842162]

26. Watanabe S, Moniaga CS, Nielsen S, Hara-Chikuma M. (2016) Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells. Biochem. Biophys. Res. Commun., 471 (1): 191-7. [PMID:26837049]

27. Yang B. (2017) Aquaporins. In Advances in Experimental Medicine and Biology Edited by Yang B (Springer) 1-276. [ISBN:9789402410570]

28. Yang B, Verkman AS. (1997) Water and glycerol permeabilities of aquaporins 1-5 and MIP determined quantitatively by expression of epitope-tagged constructs in Xenopus oocytes. J. Biol. Chem., 272 (26): 16140-6. [PMID:9195910]

Subcommittee members: Alex C. Conner (Chairperson) Institute of Clinical Sciences University of Birmingham Edgbaston Birmingham B15 2TT UK Roslyn Bill Associate Dean of Research Aston University Birmingham Philip Kitchen Aston University Birmingham Mootaz Salman Department of Cell Biology Harvard Medical School Boston, MA 02115