(Na+-K+)-ATPase inhibitors: Implications for new drug discovery

The (Na⁺-K⁺)-ATPase is a ubiquitous membrane-bound enzyme that actively transports Na⁺ out of the cell in exchange for a smaller ratio of extracellular K⁺. The current report focuses on the role of modifiers of (Na⁺-K⁺)-ATPase activity in the development of new pharmacological agents. More versatile biological test systems are proposed. Possible use of Na⁺-K⁺-ATPase activity modulators in treatment of hypertension and other diseases are discussed. It is concluded that the ubiquitous distribution and crucial role of the enzyme in normal and diseased cell function merits a critical biological and chemical reappraisal of the enzyme beyond the current narrow viewpoint dealing with the application of glycosides in the treatment of congestive heart failure.