Aldosterone enhances renal calcium reabsorption by two types of channels

Kidney Int. 2004 Jul;66(1):242-50. doi: 10.1111/j.1523-1755.2004.00725.x.

Abstract

Background: Aldosterone has been known for many years to increase sodium (Na(+)) reabsorption by the distal nephron. The present in vitro experiments investigated the effect of the hormone on calcium (Ca(2+)) transport by the luminal membrane of the rabbit nephron, independent of any systemic influence.

Methods: Proximal and distal tubules were incubated with either aldosterone or the carrier. The luminal membranes of these tubules were purified, vesiculated, and (45)Ca uptake by these vesicles was subsequently measured.

Results: Treatment of the distal tubules with 10(-8) mol/L aldosterone enhanced both 0.1 and 0.5 mmol/L Ca(2+) transport. The hormone action was abolished by tyrosine kinase inhibitors. The presence of Na(+) in the medium decreased both Ca(2+) uptake and the effect of aldosterone. This hormone action was already significant after a 5-minute incubation, with a half-maximal efficient concentration of approximately 10(-10) mol/L. Ca(2+) transport by the distal membranes presents a dual kinetics. Aldosterone enhanced the Vmax values of both components of these kinetics. Mibefradil abolished the action of aldosterone on 0.5 mmol/L but not on 0.1 mmol/L Ca(2+) uptake, suggesting that the targeted low affinity channel belongs to the T-type, whereas diltiazem prevented the hormone action exclusively at the low Ca(2+) concentration (0.1 mmol/L), indicating an effect on a high affinity L-type channel.

Conclusion: Aldosterone increases Ca(2+) transport by the distal luminal membranes through L- and T-type Ca(2+) channels, and this action requires tyrosine kinase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption / drug effects
  • Aldosterone / pharmacology*
  • Animals
  • Biological Transport / drug effects
  • Calcium / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Calcium Channels, T-Type / metabolism*
  • Canrenone / pharmacology
  • Cycloheximide / pharmacology
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Kidney Tubules, Distal / drug effects
  • Kidney Tubules, Distal / metabolism
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism
  • Kinetics
  • Membranes / drug effects
  • Membranes / metabolism
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Rabbits
  • Second Messenger Systems / physiology
  • Sodium / metabolism
  • Spironolactone / pharmacology
  • Time Factors

Substances

  • Calcium Channels, L-Type
  • Calcium Channels, T-Type
  • Mineralocorticoid Receptor Antagonists
  • Protein Synthesis Inhibitors
  • Spironolactone
  • Aldosterone
  • Canrenone
  • Cycloheximide
  • Sodium
  • Calcium