AQUAPORIN-1 IN PLASMA-MEMBRANE AND CAVEOLAE PROVIDES MERCURY-SENSITIVE WATER CHANNELS ACROSS LUNG ENDOTHELIUM

Classically, water transport across endothelium of the continuous type found in the microvessels of many organs such as lung was thought to occur almost completely via the paracellular pathway through intercell ular junctions. Direct transmembrane and transcellular transport was c onsidered to be minimal. In this study, we focused on the critical tra nsport interface in direct contact with the circulating blood by purif ying luminal endothelial cell plasma membranes directly from rat lungs and then isolating the noncoated plasmalemmal vesicles or caveolae fr om these membranes. Immunoblotting of these fractions showed that the transmembrane water channel protein aquaporin-1 was amply expressed on the endothelial cell surface at levels comparable to rat erythrocyte plasma membranes. It was found concentrated, but not exclusively in ca veolae. The functional role of these mater channels in transport was e xamined in rat lungs perfused in situ with tritiated water by testing known inhibitors of aquaporin-1-mediated transmembrane water transport . Mercurial sulfhydryl reagents such as HgCl2 reversibly reduced triti ated water uptake without affecting small solute transport. Just like certain epithelia, endothelia might express physiologically relevant a mounts of aquaporin-1 on their cell surface to permit direct, mercuria l-sensitive, transcellular transport of water.