Project: Research project

Project Details


Acid-base and chloride balance are maintained primarily by the kidney;
final regulation of urinary acid-base and chloride composition is achieved
by the collecting duct system. Bicarbonate and chloride transport by the
collecting tubule appear to be regulated by Beta-adrenergic agents and
chronically in response to systemic acid-base disturbances. The present
proposal addresses the mechanisms of acute and chronic regulation of anion
transport using isolated, perfused tubules and cultured collecting tubule
cells. The methods used include ion fluxes, electrophysiologic
measurements, and immunocytochemistry. The first specific aim is to
examine several possible mechanisms by which cyclic AMP stimulates HCO3
reabsorption in both perfused tubules and cultured cells. The hypotheses
examined include insertion of H+-pumps into the apical cell membrane,
increasing a basolateral membrane C1 conductance, or regulating the
insertion of a C1-HCO3 exchange protein into the basolateral membrane. The
second specific aim looks at the mechanisms by which in vivo acid-base
disturbances chronically regulate anion transport in intact collecting
tubule cells. The approach is a combination of functional flux
measurements on perfused tubules and both light and electron microscopical
quantitation of various anion transport cell types. The two opposing
hypotheses being tested are that reversal of net bicarbonate transport
either occurs by differential stimulation/suppression of two different
vectorally-fixed cell types or it occurs via reversal of the anion
transporting components of individual collecting tubule cells. The third
aim is to functionally and cytochemically characterize anion-transporting
cells in tissue culture. The last aim is to use these cultured
anion-transporting cells to study the mechanisms by which systemic
acid-base disturbances such as metabolic and respiratory acidosis and
alkalosis cause chronic regulation of collecting duct anion transport. The
results in cultured cells will be compared to preceding results in intact
tubules. These studies will be directly important for our understanding of
such disease states as renal tubular acidosis and metabolic alkalosis, as
well as for an understanding of renal compensatory mechanisms in
respiratory acidosis and alkalosis.
Effective start/end date12/31/894/30/95


  • Cell Biology
  • Nephrology
  • Medicine(all)


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