New steroidal digitalis-like compounds in human cataractous lenses

Since Na+/K+-ATPase has a high-affinity receptor for digitalis steroids, it has been postulated that there are endogenous ligands for these receptors which regulate the Na+/K+-pump activity. Indeed, based on their ability to inhibit 3H-ouabain binding and Na+/K+-ATPase activity, digitalis-like compounds (DLC) have been shown to be present in the brain, heart, adrenal, plasma, cerebrospinal fluid and urine of mammals and in the skin and plasma of toads (for review see 3,6,11). Several substances have been proposed as the DLC, including unsaturated fatty acids, lysophosphatidyl choline, dopamine, dehydroepiandrosterone sulfate, lignans and ascorbic acid (11). However, none of these compounds appears to be the natural ligand of the digitalis receptor of the Na+/K+-ATPase because of their limited specificity and affinity. Bufodienolides, which resemble the structure of the plant cardiac glycosides, have been identified in the plasma, brain and other tissues of toads (4,12), however their presence in mammals has not yet been demonstrated. Recently, ouabain (7) and digoxin (5) have been identified in mammalian tissues.