title: Recent concepts concerning the renal handling of NH3/NH4+.
abstract: 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 accumulate in the medullary interstitium, and finally be secreted in the medullary collecting ducts. Each of the various steps of this particular renal pathway is highly regulated, and the control of gene expression explains how the renal handling of NH 4 + becomes fully adapted to chronic acid-base changes. Several targets have been identified to account for the adaptation of renal NH 4 + synthesis and transport in response to an acid load. These are the key enzymes of ammoniagenesis and the apical Na+/H+ (NH4+) exchanger NHE3 in the proximal tubule, the apical Na + -K + (NH 4 + )-2Cl - cotransporter of the MTAL, and the basolateral Na+-K+ (NH4+)-2Cl- cotransporter and the epithelial Rh B and C glycoproteins in the collecting ducts. An acid pH appears to be a major factor in the control of gene expression during metabolic acidosis probably through the activation of pH sensors. Glucocorticoids can contribute to coordinate the adaptation of various tubular cell types. This review focuses on some new aspects of NH3/NH4+ transport and of gene expression regulation that have recently emerged.
authors.affiliation: INSERM U426, Faculty of Medicine Xavier Bichat, Paris Cedex 18, Paris, France.
authors.forename: Z
authors.initials: Z
authors.lastname: Karim
authors.forename: M
authors.initials: M
authors.lastname: Szutkowska
authors.forename: C
authors.initials: C
authors.lastname: Vernimmen
authors.forename: M
authors.initials: M
authors.lastname: Bichara
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology*; D000818:Animals; D017136:Ion Transport / Q000502:physiology; D007684:Kidney Tubules / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D000644:Quaternary Ammonium Compounds; D027981:Symporters