Cardiac Glycosides in Human Physiology and Disease: Update for Entomologists

Cardiac glycosides, cardenolides and bufadienolides, are elaborated by several plant or animal species to prevent grazing or predation. Entomologists have characterized several insect species that have evolved the ability to sequester these glycosides in their tissues to reduce their palatability and, thus, reduce predation. Cardiac glycosides are known to interact with the sodium- and potassium-activated adenosine triphosphatase, or sodium pump, through a specific receptor-binding site. Over the last couple of decades, and since entomologic studies, it has become clear that mammals synthesize endogenous cardenolides that closely resemble or are identical to compounds of plant origin and those sequestered by insects. The most important of these are ouabain-like compounds. These compounds are essential for the regulation of normal ionic physiology in mammals. Importantly, at physiologic picomolar or nanomolar concentrations, endogenous ouabain, a cardenolide, stimulates the sodium pump, activates second messengers, and may even function as a growth factor. This is in contrast to the pharmacologic or toxic micromolar or milimolar concentrations achieved after consumption of exogenous cardenolides (by consuming medications, plants, or insects), which inhibit the pump and result in either a desired medical outcome, or the toxic consequence of sodium pump inhibition.