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BENCH SCIENCE REVIEW |
Division of Nephrology,1 Université catholique de Louvain Medical School, Brussels, Belgium; Discipline of Physiology,2 School of Medical Sciences, University of Adelaide, Adelaide, Australia
Correspondence to: O. Devuyst, Division of Nephrology, UCL Medical School, 10 Avenue Hippocrate, B-1200 Brussels, Belgium. Olivier.Devuyst{at}uclouvain.be
ABSTRACT
Peritoneal dialysis involves diffusive and convective transport and
osmosis through the highly vascularized peritoneal membrane. Several lines of
evidence have demonstrated that the water channel aquaporin-1 (AQP1)
corresponds to the ultrasmall pore predicted by the model of peritoneal
transport. Proof-of-principle studies have shown that upregulation of the
expression of AQP1 in peritoneal capillaries results in increased water
permeability and ultrafiltration, without affecting the osmotic gradient or
small solute permeability. Conversely, studies in Aqp1 mice have
shown that haplo-insufficiency for AQP1 results in significant attenuation of
water transport. Recent studies have demonstrated that AQP1 is involved in the
migration of different cell types, including endothelial cells. In parallel,
chemical screening has identified lead compounds that could act as antagonists
or agonists of AQPs, with description of putative binding sites and potential
mechanisms of gating the water channel. By modulating water transport, these
pharmacological agents could have clinically relevant effects in targeting
specific tissues or disease states.
KEY WORDS: Aquaporin-1; water channels; agonist, antagonist; ultrafiltration; ultrasmall pore; peritoneal transport.
Received 21 January 2010; accepted 2 February 2010.
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