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Pathway Description
Eplerenone Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2020-08-10
Last Updated: 2023-10-25
Eplerenone is an oral drug used to treat conditions such as hypertension and congestive heart failure. Its main target is the collecting duct of the nephron.
In the principal cells of the collecting duct, sodium and water reabsorption occur, along with potassium excretion. The sodium channel (ENaC) transports Na+ from the tubule lumen into the principal cells, then the NA+/K+ ATPase pumps the Na+ into the interstitium where it reabsorbed into the blood. K+ ions are pumped into the principal cell from the interstitium via the Na+/K+ ATPase, then the K+ channel transports K+ from the cell into the lumen where it is excreted in urine. Water reabsorption is linked to Na+ reabsorption and occurs via the aquaporins.
Aldosterone is released from the adrenal cortex of the kidney and acts on the nephrons in the adrenal medulla. Aldosterone binds to mineralocorticoid receptors in the cytosol of the principal cells in the collecting duct. The mineralocorticoid receptors undergo dimerization and activation and move into the nucleus where they undergo transcription. Protein is then synthesized in the cytosol. This effect on gene transcription leads to an upregulation of sodium channels in the apical membrane and Na+/K+ ATPase in the basolateral membrane, aiding an increase in Na+ and water reabsorption and K+ excretion.
Eplerenone binds to the mineralocorticoid receptors in the cytosol and blocks aldosterone binding. This prevents the aldosterone effects on gene transcription, therefore, there is a decrease in Na+ channels and Na+/K+ ATPase in the membrane. Sodium reabsorption decreases, the concentration of Na+ in the lumen becomes high and as a result, water reabsorption also decreases. The effects on Na+/K+ ATPase results in reduced K+ excretion.
This effect of eplerenone is important for treating conditions like hypertension because the increased water excretion in urine leads to decreased blood plasma volume, lowering blood pressure.
Eplerenone may also have the same effect on Na+ and water reabsorption in the late distal convoluted tubule.
Side effects of taking eplerenone include hyperkalemia, hypertriglyceridemia, flu like symptoms, mastodynia, fatigue, abnormal vaginal bleeding, gynecomastia, headache, dizziness, diarrhea, abdominal pain, cough, angina, myocardial infarction.
References
Eplerenone Pathway References
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Pubmed: 24468074
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