To be appropriately excreted in urine, NH4+, the major component of urinary acid excretion, must be synthesized by proximal tubular cells, secreted into the proximal tubular fluid, reabsorbed by the medullary thick ascending limb (MTAL) to be accumulated in the medullary interstitium, and finally secreted in medullary collecting ducts. Several targets have been identified to account at the gene expression level for the adaptation of renal NH4+ synthesis and transport in response to a chronic acid load. These targets are the key enzymes of ammoniagenesis (mitochondrial glutaminase and glutamate dehydrogenase) and gluconeogenesis (phosphoenolpyruvate carboxykinase) and the Na+/H+( NH4+) exchanger NHE3 in the proximal tubule, the apical Na+-K+(NH4+)-2Cl– cotransporter of the MTAL, the basolateral Na+-K+(NH4+)-2Cl– cotransporter, and likely the epithelial Rh B and C glycoproteins in the collecting ducts. An acid pH per se appears to be a major factor in the control of the expression of these genes during metabolic acidosis probably through activation of pH sensors. Glucocorticoids may also act in concert with an acid pH to coordinate the adaptation of various tubular cell types. The present review focuses on some new aspects of NH3/ NH4+ transport and of regulations of gene expression that have recently emerged.

Keywords:
Ammonia synthesis, NH4+ urinary excretion, Acid-base balance regulation, Glucocorticoids, Angiotensin II, Na+-K+(NH4+)-2Cl– cotransporter, Gene expression, mRNA stability
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© 2005 S. Karger AG, Basel
2005
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