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Received May 5, 2004
Revised June 7, 2004
Accepted after revision July 26, 2004
1 Zentrum für Molekularbiologie der Pflanzen
* To whom correspondence should be addressed. E-mail: uwe.ludewig{at}zmbp.uni-tuebingen.de.
The liver and kidney are important tissues for ammonium (NH4+/NH3) metabolism and excretion. The Rh 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 are known for their predominance in electroneutral ammonium transport, in contrast to other tubular sites, where net NH4+ occurs. In accordance with its localization, human RhBG mediates saturable, electroneutral transport of the ammonium analog methylammonium when heterologously expressed in Xenopus oocytes. Uptake of methylammonium saturates with a Km=2.6 mM. Methylammonium uptake is inhibited by ammonium and this inhibition saturates with a Ki
3mM. Electric current measurements and intracellular pHi determinations suggest that RhBG acts as an electroneutral NH4+/H+ exchanger.
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