Aquaporin 6 is permeable to glycerol and urea

The passive water permeability ( L(p)) of AQP6 is activated by Hg(2+). Our aim was to test if L(p) was associated with a permeability to small hydrophilic molecules such as glycerol and urea. AQP6 was expressed in Xenopus laevis oocytes and activated by 0.3 mM of HgCl(2) in the bathing solution. HgCl(2) caused the oocytes to swell at a rate of about 0.3% min(-1). The L(p) of AQP6 was determined from brief additions or removals of mannitol from the bathing solution, and compared to the L(p) obtained from adding glycerol or urea. In paired experiments, L(p (mannitol)) was 2.4+/-0.1, L(p (glycerol)) 1.5+/-0.2, and L(p (urea)) 0.7+/-0.1 (units: 10(-5) cm s(-1) osmol(-1); 14 oocytes); the latter was not different from L(p)s obtained for native oocytes. The L(p)s were independent of the Hg(2+)-induced swelling and of the magnitude of the osmotic challenge (-75 to +100 mosmol). Hg(2+) stimulated the uptake of [(14)C]glycerol fivefold and [(14)C]urea twofold in AQP6-expressing oocytes. There were no significant uptakes in native oocytes nor in AQP1-expressing oocytes whether these were treated with HgCl(2) or not. We conclude that water, glycerol and urea share an aqueous pathway in AQP6.