HETEROGENEITY AND LABILITY OF ENDOGENOUS DIGITALIS-LIKE SUBSTANCES INTHE PLASMA OF THE TOAD, BUFO-MARINUS

Three major groups of endogenous digitalis-like substances (EDLS) have been identified in the plasma of the toad, Bufo marinus. One group of compounds, present in fresh plasma, is composed of chromatographicall y homogeneous polar conjugates, principally bufadienolide 3-sulfates, which exhibit relatively weak. Na+-K+-adenosinetriphosphatase (ATPase) inhibitory activity. A second and larger group of compounds, also fou nd in fresh plasma, includes chromatographically heterogeneous conjuga tes, which are effective inhibitors of Na+-K+-ATPase; these compounds possess properties similar to those of bufotoxins. The third group of EDLS consists of free unconjugated bufadienolides, which are also effe ctive Na+-K+-ATPase inhibitors. These unconjugated bufadienolides are present in relatively low concentrations in fresh toad plasma, but app reciable quantities are enzymatically generated from conjugates (belie ved to consist principally of bufotoxins) during the in vitro incubati on of plasma. We suggest that the extent to which circulating polar ED LS are enzymatically deconjugated in vivo may be important in the regu lation of the digitalis-sensitive Na+-K+-ATPase of toad brain, the onl y known digitalis-sensitive Na+-K+-ATPase in the toad.