27 January 2011 00:00 hrs.
Water channels in peritoneal dialysis.

Prof. dr. Olivier Devuyst, Physiologisches Institut, Universität Zürich, Switserland


 Prof. Peter Deen, department of Physiology, NCMLS

27-01-2011 00:00:00Europe/AmsterdamWater channels in peritoneal dialysis.

Remarks / more information:

Olivier-DevuystOne hundred years ago, Overton postulated that the diffusion of a molecule into the cell depends from its selective solubility across the cell membranes, and that the cell permeation rate is largely determined by the lipophilic nature of the molecule. This concept (the "Overton rule") has evolved over time, and it is now admitted that most molecules playing a role in physiology or pharmacology are transported across biological membranes by specialized proteins ("carriers") rather than by simple diffusion across the lipid bilayer. We will illustrate this concept by presenting recent data that point to the role of water channels ("aquaporins") in peritoneal dialysis, a technique that is increasingly used to treat patients with end-stage renal disease. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore predicted by the modelization of peritoneal transport. Proof-of-principle studies have shown that upregulation of the expression of AQP1 in peritoneal capillaries is reflected by increased water permeability and ultrafiltration, without affecting the osmotic gradient and the permeability for small solutes. Inversely, studies in Aqp1 mice have shown that haplo-insufficiency in AQP1 is reflected by significant attenuation of water transport. Recent studies have identified lead compounds that could act as agonists of aquaporins, as well as putative binding sites and potential mechanisms of gating the water channel. These studies on the peritoneal membrane also provide an experimental framework to investigate the role of water channels in the endothelium and various cell types.

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