Electroneutral ammonium transport by basolateral rhesus B glycoprotein

The liver and kidney are important tissues for ammonium (NH4+/NH3) metabolism and excretion. The rhesus B glycoprotein (RhBG) is a membrane protein expressed in liver and kidney with similarity to NH4+ transporters found in microorganisms, plants and animals. In the kidney, RhBG is predominantly localized to basolateral membranes of distal tubule epithelia, including connecting tubules and collecting ducts. These epithelia display mainly electroneutral ammonium transport, in contrast to other tubular sites, where net NH4+ transport occurs. In accordance with its localization, human RhBG mediates saturable, electroneutral transport of the ammonium analogue methylammonium when heterologously expressed in Xenopus oocytes. Uptake of methylammonium saturates with a K-m = 2.6 mM. Methylammonium uptake is inhibited by ammonium and this inhibition saturates with a K-i approximate to 3 mm. Electric current measurements and intracellular pH(i) determinations suggest that RhBG acts as an electroneutral NH4+-H+ exchanger.