Zeta-crystallin mediates the acid pH-induced increase of BSC1 cotransporter mRNA stability.

The Na+/K+/2Cl- cotransporter (BSC1/NKCC2) is the major transporter mediating sodium chloride and ammonium absorption in the medullary thick ascending limb. A loss-of-function mutation of BSC1 is responsible for Bartter's syndrome. We previously showed both in vivo and in vitro that acidosis increases the expression and activity of BSC1 and that acid pH enhances the stability of BSC1 mRNA by mechanisms involving its 3'-untranslated region (UTR).

Renal handling of NH3/NH4+: recent concepts.

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.