Selectivity of the renal collecting duct water channel aquaporin-3

Aquaporin-3 (AQP3) is a water channel found in the basolateral cell membrane of principal cells of the renal collecting tubule as well as in other epithelia. To examine the selectivity of AQP3, the permeability to water (P-f), urea (P-ur), and glycerol (P-gly) of Xenopus oocytes injected with cRNA encoding AQP3 was measured. Oocytes injected with cRNA encoding either human or rat aquaporin-1 (AQP1) were used as controls. Although both aquaporins permit water flow across the cell membrane, only AQP3 was permeable to glycerol and urea (P-gly > P-ur). The uptake of glycerol into oocytes expressing AQP3 was linear up to 165 mM. For AQP3 the Arrhenius energy of activation for P-f was 3 kcal/mol, whereas for P-gly and P-ur it was >12 kcal/mol. The sulfhydryl reagent p-chloromercuriphenylsulfonate (1 mM) abolished P-f of AQP3, whereas it did not affect P-gly. In addition, phloretin (0.1 mM) inhibited P-f of AQP3 by 35%, whereas it did not alter P-gly or P-ur. We conclude that water does not share the same pathway with glycerol or urea in AQP3 and that this aquaporin, therefore, forms a water-selective channel.