Abstract
Cardioactive glycosides, like digoxin, ouabain and related compounds, are drugs that inhibit Na+/K+-ATPase and have a strong inotropic effect on heart: they cause the Na+/Ca2+ exchanger to extrude Na+ in exchange with Ca2+ and therefore increase the [Ca2+]i concentration. For this reason, some of these drugs are currently used in the treatment of congestive heart failure and cardiac arrhythmias. Recently it has been discovered that cardiac glycosides exert pleiotropic effects on many aspects of cell metabolism. Na+/K+-ATPase is not the exclusive target, as they affect the cell response to hypoxia, modulate several signaling pathways involved in cell death and proliferation, regulate the transcription of different genes and modify the pharmacokinetics of other drugs, by altering the expression and activity of drug-metabolizing enzymes. Some of these effects are related to the steroid structure of glycosides, a property which also makes them fine modulators of the synthesis of cholesterol and steroid hormones. Moreover, new endogenously synthesized glycosides have been discovered in the last years: these molecules are involved in the balance of salt and in the control of blood pressure.
This review will focus on the recent studies which have demonstrated that exogenous and endogenous glycosides, besides playing a role as inotropic agents, are also important in the pathogenesis and therapy of different human diseases, such as stroke, diabetes, neurological diseases and cancer.
Keywords: Digoxin, ouabain, Na+/K+-ATPase, cancer, sterols metabolism, Cardioactive glycosides, cardiac arrhythmias, pleiotropic effects, roliferation
Current Medicinal Chemistry
Title: Pleiotropic Effects of Cardioactive Glycosides
Volume: 18 Issue: 6
Author(s): C. Riganti, I. Campia, J. Kopecka, E. Gazzano, S. Doublier, E. Aldieri, A. Bosia and D. Ghigo
Affiliation:
Keywords: Digoxin, ouabain, Na+/K+-ATPase, cancer, sterols metabolism, Cardioactive glycosides, cardiac arrhythmias, pleiotropic effects, roliferation
Abstract: Cardioactive glycosides, like digoxin, ouabain and related compounds, are drugs that inhibit Na+/K+-ATPase and have a strong inotropic effect on heart: they cause the Na+/Ca2+ exchanger to extrude Na+ in exchange with Ca2+ and therefore increase the [Ca2+]i concentration. For this reason, some of these drugs are currently used in the treatment of congestive heart failure and cardiac arrhythmias. Recently it has been discovered that cardiac glycosides exert pleiotropic effects on many aspects of cell metabolism. Na+/K+-ATPase is not the exclusive target, as they affect the cell response to hypoxia, modulate several signaling pathways involved in cell death and proliferation, regulate the transcription of different genes and modify the pharmacokinetics of other drugs, by altering the expression and activity of drug-metabolizing enzymes. Some of these effects are related to the steroid structure of glycosides, a property which also makes them fine modulators of the synthesis of cholesterol and steroid hormones. Moreover, new endogenously synthesized glycosides have been discovered in the last years: these molecules are involved in the balance of salt and in the control of blood pressure.
This review will focus on the recent studies which have demonstrated that exogenous and endogenous glycosides, besides playing a role as inotropic agents, are also important in the pathogenesis and therapy of different human diseases, such as stroke, diabetes, neurological diseases and cancer.
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Cite this article as:
Riganti C., Campia I., Kopecka J., Gazzano E., Doublier S., Aldieri E., Bosia A. and Ghigo D., Pleiotropic Effects of Cardioactive Glycosides, Current Medicinal Chemistry 2011; 18 (6) . https://dx.doi.org/10.2174/092986711794927685
DOI https://dx.doi.org/10.2174/092986711794927685 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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