Endogenous cardiotonic steroids (ECS) are similar to digitalis. Humans produce ECS similar to ouabain. These chemicals alter the sodium pump (Na(+)/K(+)-ATPase.) ECS regulate cell growth, differentiation, apoptosis, fibrosis, immunity, carbohydrate metabolism, and nervous and mental functions. They are involved in hypertension, preeclampsia, end-stage kidney disease, congestive heart failure, and diabetes mellitus. They can be therapeutic.
The sodium pump is an enzyme in the cell wall which maintains a gradient of sodium (Na+) and potassium (K+) across the cell wall. The pump was discovered by J. C. Skou in 1959, made possible by knowledge of the cardiotonic steroid (CTS,) ouabain. (He received a Nobel Prize.) Ouabain of plant origin is the same as endogenous CTS of animal origin. They inhibit the sodium pump. The sodium pump is necessary for nerve conduction and for muscle contraction.
The sodium pump is two polypeptides in equal amounts. It binds Na+ on the outside and K+ and ATP inside of the cell. Using ATP energy, Na+ and K+ pass each other across concentration gradients, with Na+ going to the outside of the cell and K+ ions moving to the inside of the cell. K+ ions are released inside the cell and Na+ ions are released outside the cell. By developing concentration gradients, the sodium pump generates electrical activity, concentrates urine and makes muscles contract. CTS are necessary for these processes.
Dietary sodium chloride (NaCl) is important in hypertension. The handling of urinary Na+ depends on a natural, digoxin-like sodium pump inhibitor. A number of studies “strongly implicated CTS in the pathogenesis of hypertension.”
Breast cancer patients taking digitalis had a reduced risk of cancer spread and better survival. Test tube studies show an anti-cancer effect of CTS. CTS may cause cancer, paradoxically.
CONCLUSION: Cardiotonic steroids are a major class of hormone. CTS circulate in nanomolar and subnanomolar levels. They change cell wall electrical potentials and alter blood pressures, cancer risk, apoptosis, glucose metabolism and central nervous system functions. Blocking CTS functions may be therapeutic.
Read about the effect of cardiotonic steroids on multidrug-resistant cancer cells (multi-drug.)
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