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 intercellular junctions. Direct transmembrane and transcellular transport was considered to be minimal. In this study, we focused on the critical transport interface in direct contact with the circulating blood by purifying luminal endothelial cell plasma membranes directly from rat lungs and then isolating the noncoated plasmalemmal vesicles or caveolae from 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 caveolae. The functional role of these water channels in transport was examined 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 tritiated water uptake without affecting small solute transport. Just like certain epithelia, endothelia might express physiologically relevant amounts of aquaporin-1 on their cell surface to permit direct, mercurial-sensitive, transcellular transport of water.