Distal urinary acidification from Homer Smith to the present

Kidney Int. 1996 Jun;49(6):1660-4. doi: 10.1038/ki.1996.242.


Since Smith's time, the essential role of collecting duct intercalated cells in controlling net acid excretion has been recognized. Rather than employing an H(+)-exchange mechanism, intercalated cells have V-ATPase on the plasma membrane and in plasmalemma-associated tubulovesicles, which functions in the bicarbonate reabsorption, regeneration, and bicarbonate secretion required for acid-base homeostasis. Several distinct mechanisms participate in regulating V-ATPase-driven H+ secretion in different cell types: (1) Renal epithelial cells have the capacity to express different structural forms of V-ATPase that have intrinsic differences in their enzymatic properties. 2) The kidney produces cytosolic regulatory proteins, capable of interacting directly with the V-ATPase, that may modify its activity. V-ATPases in different cell types may differ in the degree to which their activity is affected by regulatory factors, as a result of variations in V-ATPase structure. (3) In the alpha intercalated cell, the number of active V-ATPases on the luminal membrane is controlled in vivo by membrane vesicle-mediated traffic that may require unidentified mediators. In the beta intercalated cell, the number of active V-ATPases on the basolateral membrane may be controlled by regulated assembly and disassembly, responding directly to extracellular pH.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acids / urine*
  • Animals
  • History, 20th Century
  • Kidney / physiology
  • Kidney / ultrastructure
  • Kidney Tubules, Distal / physiology*
  • Nephrology / history
  • Physiology, Comparative / trends


  • Acids