AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1

Andrea J Yool, Johann Morelle, Yvette Cnops, Jean-Marc Verbavatz, Ewan M Campbell, Elizabeth A H Beckett, Grant W Booker, Gary Flynn, Olivier Devuyst

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Aquaporin-1 (AQP1) facilitates the osmotic transport of water across the capillary endothelium, among other cell types, and thereby has a substantial role in ultrafiltration during peritoneal dialysis. At present, pharmacologic agents that enhance AQP1-mediated water transport, which would be expected to increase the efficiency of peritoneal dialysis, are not available. Here, we describe AqF026, an aquaporin agonist that is a chemical derivative of the arylsulfonamide compound furosemide. In the Xenopus laevis oocyte system, extracellular AqF026 potentiated the channel activity of human AQP1 by >20% but had no effect on channel activity of AQP4. We found that the intracellular binding site for AQP1 involves loop D, a region associated with channel gating. In a mouse model of peritoneal dialysis, AqF026 enhanced the osmotic transport of water across the peritoneal membrane but did not affect the osmotic gradient, the transport of small solutes, or the localization and expression of AQP1 on the plasma membrane. Furthermore, AqF026 did not potentiate water transport in Aqp1-null mice, suggesting that indirect mechanisms involving other channels or transporters were unlikely. Last, in a mouse gastric antrum preparation, AqF026 did not affect the Na-K-Cl cotransporter NKCC1. In summary, AqF026 directly and specifically potentiates AQP1-mediated water transport, suggesting that it deserves additional investigation for applications such as peritoneal dialysis or clinical situations associated with defective water handling.
Original languageEnglish
Pages (from-to)1045-1052
Number of pages8
JournalJournal of the American Society of Nephrology
Volume24
Issue number7
Early online date6 Jun 2013
DOIs
Publication statusPublished - 28 Jun 2013

Fingerprint

Aquaporin 1
Aquaporins
Peritoneal Dialysis
Water
Sodium-Potassium-Chloride Symporters
Pyloric Antrum
Furosemide
Vascular Endothelium
Xenopus laevis
Ultrafiltration
Human Activities
Oocytes
AqF026
Binding Sites
Cell Membrane
Membranes

Cite this

Yool, A. J., Morelle, J., Cnops, Y., Verbavatz, J-M., Campbell, E. M., Beckett, E. A. H., ... Devuyst, O. (2013). AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1. Journal of the American Society of Nephrology, 24(7), 1045-1052. https://doi.org/10.1681/ASN.2012080869

AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1. / Yool, Andrea J; Morelle, Johann; Cnops, Yvette; Verbavatz, Jean-Marc; Campbell, Ewan M; Beckett, Elizabeth A H; Booker, Grant W; Flynn, Gary; Devuyst, Olivier.

In: Journal of the American Society of Nephrology, Vol. 24, No. 7, 28.06.2013, p. 1045-1052.

Research output: Contribution to journalArticle

Yool, AJ, Morelle, J, Cnops, Y, Verbavatz, J-M, Campbell, EM, Beckett, EAH, Booker, GW, Flynn, G & Devuyst, O 2013, 'AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1', Journal of the American Society of Nephrology, vol. 24, no. 7, pp. 1045-1052. https://doi.org/10.1681/ASN.2012080869
Yool, Andrea J ; Morelle, Johann ; Cnops, Yvette ; Verbavatz, Jean-Marc ; Campbell, Ewan M ; Beckett, Elizabeth A H ; Booker, Grant W ; Flynn, Gary ; Devuyst, Olivier. / AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1. In: Journal of the American Society of Nephrology. 2013 ; Vol. 24, No. 7. pp. 1045-1052.
@article{ce3cbbe6b98446589b335f17b76c0a97,
title = "AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1",
abstract = "Aquaporin-1 (AQP1) facilitates the osmotic transport of water across the capillary endothelium, among other cell types, and thereby has a substantial role in ultrafiltration during peritoneal dialysis. At present, pharmacologic agents that enhance AQP1-mediated water transport, which would be expected to increase the efficiency of peritoneal dialysis, are not available. Here, we describe AqF026, an aquaporin agonist that is a chemical derivative of the arylsulfonamide compound furosemide. In the Xenopus laevis oocyte system, extracellular AqF026 potentiated the channel activity of human AQP1 by >20{\%} but had no effect on channel activity of AQP4. We found that the intracellular binding site for AQP1 involves loop D, a region associated with channel gating. In a mouse model of peritoneal dialysis, AqF026 enhanced the osmotic transport of water across the peritoneal membrane but did not affect the osmotic gradient, the transport of small solutes, or the localization and expression of AQP1 on the plasma membrane. Furthermore, AqF026 did not potentiate water transport in Aqp1-null mice, suggesting that indirect mechanisms involving other channels or transporters were unlikely. Last, in a mouse gastric antrum preparation, AqF026 did not affect the Na-K-Cl cotransporter NKCC1. In summary, AqF026 directly and specifically potentiates AQP1-mediated water transport, suggesting that it deserves additional investigation for applications such as peritoneal dialysis or clinical situations associated with defective water handling.",
author = "Yool, {Andrea J} and Johann Morelle and Yvette Cnops and Jean-Marc Verbavatz and Campbell, {Ewan M} and Beckett, {Elizabeth A H} and Booker, {Grant W} and Gary Flynn and Olivier Devuyst",
year = "2013",
month = "6",
day = "28",
doi = "10.1681/ASN.2012080869",
language = "English",
volume = "24",
pages = "1045--1052",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "7",

}

TY - JOUR

T1 - AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1

AU - Yool, Andrea J

AU - Morelle, Johann

AU - Cnops, Yvette

AU - Verbavatz, Jean-Marc

AU - Campbell, Ewan M

AU - Beckett, Elizabeth A H

AU - Booker, Grant W

AU - Flynn, Gary

AU - Devuyst, Olivier

PY - 2013/6/28

Y1 - 2013/6/28

N2 - Aquaporin-1 (AQP1) facilitates the osmotic transport of water across the capillary endothelium, among other cell types, and thereby has a substantial role in ultrafiltration during peritoneal dialysis. At present, pharmacologic agents that enhance AQP1-mediated water transport, which would be expected to increase the efficiency of peritoneal dialysis, are not available. Here, we describe AqF026, an aquaporin agonist that is a chemical derivative of the arylsulfonamide compound furosemide. In the Xenopus laevis oocyte system, extracellular AqF026 potentiated the channel activity of human AQP1 by >20% but had no effect on channel activity of AQP4. We found that the intracellular binding site for AQP1 involves loop D, a region associated with channel gating. In a mouse model of peritoneal dialysis, AqF026 enhanced the osmotic transport of water across the peritoneal membrane but did not affect the osmotic gradient, the transport of small solutes, or the localization and expression of AQP1 on the plasma membrane. Furthermore, AqF026 did not potentiate water transport in Aqp1-null mice, suggesting that indirect mechanisms involving other channels or transporters were unlikely. Last, in a mouse gastric antrum preparation, AqF026 did not affect the Na-K-Cl cotransporter NKCC1. In summary, AqF026 directly and specifically potentiates AQP1-mediated water transport, suggesting that it deserves additional investigation for applications such as peritoneal dialysis or clinical situations associated with defective water handling.

AB - Aquaporin-1 (AQP1) facilitates the osmotic transport of water across the capillary endothelium, among other cell types, and thereby has a substantial role in ultrafiltration during peritoneal dialysis. At present, pharmacologic agents that enhance AQP1-mediated water transport, which would be expected to increase the efficiency of peritoneal dialysis, are not available. Here, we describe AqF026, an aquaporin agonist that is a chemical derivative of the arylsulfonamide compound furosemide. In the Xenopus laevis oocyte system, extracellular AqF026 potentiated the channel activity of human AQP1 by >20% but had no effect on channel activity of AQP4. We found that the intracellular binding site for AQP1 involves loop D, a region associated with channel gating. In a mouse model of peritoneal dialysis, AqF026 enhanced the osmotic transport of water across the peritoneal membrane but did not affect the osmotic gradient, the transport of small solutes, or the localization and expression of AQP1 on the plasma membrane. Furthermore, AqF026 did not potentiate water transport in Aqp1-null mice, suggesting that indirect mechanisms involving other channels or transporters were unlikely. Last, in a mouse gastric antrum preparation, AqF026 did not affect the Na-K-Cl cotransporter NKCC1. In summary, AqF026 directly and specifically potentiates AQP1-mediated water transport, suggesting that it deserves additional investigation for applications such as peritoneal dialysis or clinical situations associated with defective water handling.

U2 - 10.1681/ASN.2012080869

DO - 10.1681/ASN.2012080869

M3 - Article

C2 - 23744886

VL - 24

SP - 1045

EP - 1052

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 7

ER -