The Rh gene family and renal ammonium transport

Renal acid-base homeostasis, to a very large extent, depends on renal ammonia production and transport. A putative ammonia transporter family of proteins has recently been identified, and at least two members of this family are expressed in the renal connecting segment and collecting duct. The purpose of this review is to discuss key features of renal ammonia metabolism and transport, with particular emphasis on the transporters involved in this process.

The putative ammonia transporter family members, RhBG and RhCG, are expressed in the renal connecting segment and collecting duct. Basolateral RhBG is expressed by all cells in the connecting segment and cortical collecting duct, and by intercalated cells in the outer medullary and inner medullary collecting duct. Apical RhCG is expressed in the same distribution and also in the outer stripe of the outer medullary collecting duct principal cells. In all regions, the expression of RhBG and RhCG is greater in intercalated cells than in principal cells. The related protein, RhAG, appears to be an erythroid-specific protein that mediates ammonium/hydrogen ion (NH4/H) exchange. RhBG and RhCG appear to be sodium and potassium ion-independent ammonia transporters. Whether they mediate electrogenic ammonia transport or electroneutral ammonia/hydrogen ion exchange remains an active area of investigation. Finally, transport studies have identified that electroneutral ammonium/hydrogen ion exchange is present in the collecting duct.

The Rh glycoproteins, RhBG and RhCG, appear to mediate important roles in renal ammonia transport, and therefore in acid-base homeostasis.