Effect of ouabain on calcium signaling in rodent brain: A systematic review of studies.

The Na/K-ATPase is an integral membrane ion pump, essential to maintaining osmotic balance in cells in the presence of cardiotonic steroids; more specifically, ouabain can be an endogenous modulator of the Na/K-ATPase. Here, we conducted a systematic review of the effects of cardiotonic steroids on Ca in the brain of rats and mice. Methods: The review was carried out using the PubMed, Virtual Health Library, and EMBASE databases (between 12 June 2020 and 30 June 2020) and followed the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).

Mechanisms associated to impaired activity of cardiac P-type ATPases in endothelial nitric oxide synthase knockout mice.

The effect of long-lasting in vivo restriction of nitric oxide (NO) bioavailability on cardiac and renal P-type ATPases critical for intracellular ion homeostasis is controversial. Previous work has shown in eNOS knockout (eNOS(-/-)) mice hearts that Na(+)/K(+)- and Ca(2+)-ATPase activities were depressed but the underlying mechanisms are still unclear. The goal of this study was to characterize potential alterations responsible for impaired enzyme activity in eNOS(-/-) mice.

Natriuretic effect of bufalin in isolated rat kidneys involves activation of the Na+-K+-ATPase-Src kinase pathway.

Bufadienolides are structurally related to the clinically relevant cardenolides (e.g., digoxin) and are now considered as endogenous steroid hormones.

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.

Insights into the mechanism of Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan.

The molecular mechanisms involved in Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan were investigated. We show that this compound decreases the free sulfydryl groups present in the enzyme and that its inhibitory effect is prevented by dithiothreitol and other two sulfydryl containing reagents. We propose a redox cycle culminating with the irreversible oxidation of sulfydryl groups essential for the catalytic activity of this enzyme and of two other related P-type ATPases.

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.

Structure-activity relationship of wedelolactone analogues: structural requirements for inhibition of Na+, K+ -ATPase and binding to the central benzodiazepine receptor.

Coumestans 2a-i, bearing different patterns of substitution in A- and D-rings, were synthesized and evaluated as inhibitors of kidney Na+, K+ -ATPase and ligands for the central benzodiazepine (BZP) receptor. The presence of a hydroxyl group in position 2 favours the effect on Na+, K+ -ATPase but decreases the affinity for the BZP receptor, allowing the design of more selective molecules than the natural wedelolactone. On the other hand, the presence of a catechol in ring D is important for the effect on both molecular targets.

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.