The erythrophleum alkaloid cassaine shares many of the pharmacological actions of the cardiac glycosides but lacks the structural characteristics typical of cardiac glycosides. To further investigate the relationship between Na++K+-ATPase inhibition and the cardiotonic actions of these drugs we investigated the interaction of cassaine with the Na++K+-ATPase. Cassaine inhibited rat brain Na++K+-ATPase with about one quarter of the apparent affinity of ouabain for this enzyme. This inhibition was non-competitive with respect to K+. Cassaine also inhibited this enzyme in the presence of Mg2+ and this inhibition was enhanced by Pi and antagonized by Na+. In the presence of Na+, Mg2+ and (γ-32P)-ATP cassaine acted to stabilize the phosphorylated intermediate of Na++K+-ATPase. Cassaine also acted to displace specifically bound (3H)-ouabain from this enzyme. These observations suggested that cassaine inhibited the Na++K+-ATPase by interacting at the cardiotonic steroid binding sites of Na++K+-ATPase. Consistent with this hypothesis, dog, guinea pig and rat heart Na++K+-ATPase showed differing sensitivities to cassaine paralleling their differing sensitivities to ouabain. The principal difference between the interaction of cassaine and ouabain with Na++K+-ATPase appeared to be the more rapid dissociation of cassaine from the cardiotonic steroid binding site(s) of Na++K+-ATPase. In keeping with this the rates of offset of cassaine-induced inotropy in Langendorff perfused dog and guinea pig hearts were several times faster than those of ouabain-induced inotropy.
|Number of pages||13|
|Journal||European Journal of Pharmacology|
|State||Published - 1975|
- Cardiac tissue
- Phosphorylated intermediate