Recent Advances in Understanding Renal Ammonia Metabolism and Transport

I. David Weiner; Jill W. Verlander

Disclosures

Curr Opin Nephrol Hypertens. 2016;25(5):436-443. 

In This Article

Advances in Ammonia Transport

Collecting duct ammonia secretion involves parallel NH3 and H+ transport, with little-to-no NH4+ permeability.[33,34] H+ secretion involves H+-ATPase and H+-K+-ATPase. The Rhesus (Rh) glycoproteins, Rhbg and Rhcg, in addition to basolateral Na+-K+-ATPase in the inner medullary collecting duct, are involved directly in ammonia transport.[4,35] Fig. 6 shows a current model of collecting duct ammonia secretion.

Figure 6.

Model of collecting duct ammonia secretion. Ammonia uptake across the basolateral plasma membrane primarily involves transporter-mediated uptake by either Rhbg or Rhcg, with a component of diffusive NH3 absorption. Cytosolic NH3 is transported across the apical plasma membrane by a combination of Rhcg and diffusive transport. Not shown is that in the inner medullary collecting duct, but not the cortical collecting duct, basolateral plasma membrane Na+-K+-ATPase also contributes to basolateral NH4 + uptake. Cytosolic H+ is generated by a carbonic anhydrase-II mediated mechanism, and is secreted across the apical plasma membrane via H+-ATPase and H+-K+-ATPase. Luminal H+ titrates luminal NH3, forming NH4 + and maintaining a low luminal NH3 concentration necessary for NH3 secretion. Reproduced with permission [35].

Molecular Aspects of Rh Glycoprotein Ammonia Transport

The molecular forms of ammonia, NH3 versus NH4+, that Rh glycoproteins transport, continue to be actively investigated. One important finding from recent studies is the identification that results using the ammonia analogue, methylammonia, may not accurately predict results for ammonia.[36] A second important finding is that Rhbg, as does the erythroid-specific Rh glycoprotein, Rhag, primarily transports ammonia in the molecular form of NH4+, but there may be a small component of NH3 transport.[36] Rhcg, in contrast, primarily appears to transport NH3, with no detectable NH4+ transport capability.[36]

The difference in ammonia species transported by Rhbg and Rhcg is important in their role in collecting duct ammonia secretion. Rhbg is present in collecting duct basolateral plasma membrane, and its electrogenic transport of NH4 + results in a greater electrochemical gradient for uptake than would occur for NH3 transport. Rhcg's transport of NH3 rather than NH4 + is critical for Rhcg to facilitate apical ammonia secretion. Specifically, the low luminal pH and the high pKa' of the NH3 + H+ [left right arrow] NH4 + buffer reaction keep luminal [NH3] low, facilitating apical NH3 secretion. Electrogenic NH4 + secretion via Rhcg would be unlikely to occur because the high luminal [NH4 +] in combination with intracellular electronegativity would cause the electrochemical gradient for NH4 + movement to be from lumen to cytoplasm, that is, reabsorption, not secretion. Thus, the differential specificities of Rhbg and Rhcg for NH3 and NH4 + contribute to collecting duct ammonia secretion.

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