Inhibitory effect of combinations of digoxin and endogenous cardiotonic steroids on Na+/K+-ATPase activity in human kidney membrane preparation.

Aims: Cardiac glycosides have been extensively used in the treatment of congestive heart failure for more than 200 years. Recently, cardenolides and bufadienolides were isolated from mammalian tissue and are considered as a new class of steroidal hormones. The aim of the present work was to characterize the interaction between the most clinical used cardiac glycoside digoxin and the cardiac glycosides known to exist endogenously, i.

Synergistic interaction between ouabain and 8-methoxy-3,9-dihydroxy coumestan, a non-steroidal synthetic inhibitor of Na+,K+-ATPase.

The use of combination drugs is very common in therapeutics as in the treatment of infectious diseases, cancer and heart failure but controversies about analysis of these interactions are frequent. The aim of the present work was to characterize the interaction between ouabain and 8-methoxy-3,9-dihydroxy coumestan (LQB93), a non-steroidal synthetic inhibitor of Na+,K+-ATPase, as well as the interaction between ouabain and ouabagenin, two cardiac glycosides sharing the same binding site. Inhibition of rat kidney Na+,K+-ATPase with increasing concentrations of the drugs alone or of mixtures of ouabain:ouabagenin and LQB93:ouabain in a fixed 1:4 ratio was performed.

2-Methoxy-3,8,9-trihydroxy coumestan: a new synthetic inhibitor of Na+,K+-ATPase with an original mechanism of action.

The aim of the present work was to analyse the interaction between Na(+),K(+)-ATPase and one of our recent synthesized coumestans, namely the original molecule 2-methoxy-3,8,9-trihydroxy coumestan (PCALC36). Rat brain (mainly alpha 2 and alpha 3 Na(+),K(+)-ATPase isoforms) and kidney (alpha 1 isoform) fractions enriched with Na(+),K(+)-ATPase were utilized to compare the inhibition promoted by PCALC36 with that of classical inhibitors like ouabain and vanadate. Analysis of inhibition curves revealed that unlike ouabain, which was about a thousand times more potent to inhibit brain isoforms than kidney isoform, PCALC36 had a similar affinity for brain (IC(50)=4.