This study investigated the ability of the renal Na+-dicarboxylate cotransp
orter, NaDC-1, to transport water. Rabbit NaDC-1 was expressed in Xenopus l
aevis oocytes, cotransporter activity was measured as the inward current ge
nerated by substrate (citrate or succinate), and water transport was monito
red by the changes in oocyte volume. In the absence of substrates, oocytes
expressing NaDC-1 showed an increase in osmotic water permeability, which w
as directly correlated with the expression level of NaDC-1. When NaDC-1 was
transporting substrates, there was a concomitant increase in oocyte volume
. This solute-coupled influx of water took place in the absence of, and eve
n against, osmotic gradients. There was a strict stoichiometric relationshi
p between Na+, substrate, and water transport of 3 Na+, 1 dicarboxylate, an
d 176 water molecules/transport cycle. These results indicate that the rena
l Naf-dicarboxylate cotransporter mediates water transport and, under physi
ological conditions, may contribute to fluid reabsorption across the proxim
al tubule.