Institute of Physiology, University of Zürich, Zürich, Switzerland.
J Nephrol. 2010 Nov-Dec;23 Suppl 16:S170-4.
Peritoneal dialysis involves diffusive and convective transports 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 modelization of peritoneal transport. Proof-of-principle studies have shown that up-regulation 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 haploinsufficiency 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. By modulating water transport, these pharmacological agents could have clinically relevant effects in targeting specific tissues or disease states. 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.
腹膜透析涉及通过高度血管化的腹膜进行弥散和对流转运以及渗透。有几条证据表明,水通道蛋白 aquaporin-1(AQP1)与腹膜转运模型预测的超小孔相对应。原理验证研究表明,AQP1 在腹膜毛细血管中的表达上调反映了水通透性和超滤的增加,而不会影响渗透梯度和小溶质的通透性。相反,在 Aqp1 小鼠中的研究表明,AQP1 的单倍不足反映了水转运的显著衰减。最近的研究已经确定了可能作为水通道蛋白激动剂的先导化合物,以及潜在的结合位点和水通道的潜在门控机制。通过调节水转运,这些药物在针对特定组织或疾病状态时可能具有临床相关的效果。这些对腹膜的研究也为研究水通道在血管内皮和各种细胞类型中的作用提供了实验框架。