Renal handling of NH4+ in relation to the control of acid-base balance by the kidney.
The major component of urinary acid excretion is NH4+. To be appropriately excreted in urine, NH4+ 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. Each step of this renal pathway is highly regulated and, in addition to acute events mediated by peptide hormones such as parathyroid hormone, the control of gene expression explains how the renal handling of NH4+ fully adapts to chronic changes in the acid-base status. Several targets have been identified at the gene expression level to account for the adaptation of renal NH4+ synthesis and transport in response to an acid load. These are the key enzymes of ammoniagenesis (mitochondrial glutaminase and glutamate dehydrogenase) and gluconeogenesis (phosphoenolpyruvate carboxykinase) in the proximal tubule, the apical Na(+)-K+(NH4+)-2Cl- cotransporter of the MTAL, and the basolateral Na(+)-K+(NH4+)-2Cl- cotransporter of medullary collecting ducts. At least two factors control the expression of these genes during metabolic acidosis: an acid pH and glucocorticoids, which appear to act in concert to coordinate the adaptation of various tubular cell types. The present review focuses on some aspects of these regulations that have been recently elucidated.
Karim
Zoubida
Z
INSERM U.426, Institut Fédératif Régional Claude Bernard, Faculté de Médecine Xavier Bichat, Université Paris 7, France.
Attmane-Elakeb
Amel
A
Bichara
Maurice
M
D000136:Acid-Base Equilibrium / Q000502:physiology*; D000818:Animals; D007668:Kidney / Q000502:physiology*; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*
D000644:Quaternary Ammonium Compounds