Spironolactone Pathway


Spironolactone is a potassium-sparing diuretic. It acts by competing with aldosterone for its receptor inside the principal cells of the late distal tubule and collecting tubule. Aldosterone increases sodium reabsorption and potassium excretion by up-regulating the expression of basolateral sodium-potassium ATPases as well as luminal (apical) sodium and potassium channels. Sodium in the nephron lumen enters the principal cells through the luminal sodium channels, where it is then actively pumped out into the interstitium by sodium-potassium ATPases. This causes the interstitium to become hyperosmotic and establishes an osmotic gradient, facilitating water reabsorption through aquaporin channels. On the other hand, potassium is actively pumped from the interstitium into the principle cell. It then diffuses from inside the cell into the nephron lumen via potassium channel, driven by an electrochemical gradient established by sodium leaving the lumen. Potassium entering the nephron lumen is subsequently excreted in the urine. Spironolactone inhibits sodium and water reabsorption as well as potassium excretion by blocking the actions of aldosterone as described above.

Pathway legend Zoom in Zoom out

Pathway Image

Pathway legend Zoom in Zoom out

References

  1. Brater, D.C. (2000). Pharmacology of diuretics. American Journal of Medical Sciences, 319(1), 38-50. PMID: 10653443
  2. Davies, D.L., & Wilson, G.M. (1975). Diuretics: mechanism of action and clinical application. Drugs, 9(3), 178-226. PMID: 1092541