Discovery of Endogenous Ouabain — A New Mammalian Hormone

Abstract

Cardiac glycosides and their aglycones have been used widely in the therapy of shock and congestive heart failure (13,23). It is generally believed that the therapeutic actions of this class of compounds are secondary to their specific interaction with a conserved receptor site on the Na⁺/K⁺-pump. Speculation that there may be an endogenous mammalian counterpart to the cardiac glycosides can be traced back more than a century and has been repeated often (26). However, most of the evidence for the existence of such a factor has been fragmentary and based primarily upon bioassay or other indirect data. Despite the fact that enormous progress has been made in the chromatographic and analytical sciences in the last thirty years, nothing was known about the general class of compounds to which this factor may belong or the manner in which this inhibitor interacts with the Na⁺/K⁺-pump. The following is an account of the purification and identification of an Na⁺/K⁺-pump inhibitor from human plasma that was carried out in collaboration with The Upjohn Company.