title: High sensitivity of the Na+, K+-pump of human red blood cells to genins of cardiac glycosides.
abstract: 1. Four different cardiac glycosides (ouabain, digitoxin, digoxin and gitoxin) and their corresponding genins were tested on Na+, K+-pump fluxes measured under steady-state and initial rate conditions (non equilibrium conditions) in human and rat erythrocytes and in mouse macrophages. 2. In human red cells, Na+, K+-pump fluxes exhibited up to 8 fold higher sensitivity to genins than to glycosides. In addition genins, but not the corresponding glycosides, exhibited double reactivity with regard to the erythrocyte Na+, K+-pump (with the exception of gitoxigenin). A weak reactivity component was similar to the one of the corresponding glycosides (IC50 of about 10(-6) M) and a high reactivity component exhibited IC50 values varying from 0.1 to 0.5 X 10(-6) M for digitoxigenin and ouabagenin respectively. 3. In contrast with human red cells, the initial rate of Na+, K+-pump fluxes in rat erythrocytes and mouse macrophages was less sensitive to genins than to the corresponding cardiac glycosides. 4. Dihydroouabain was 3, 10 and 75 times less active than ouabain in inhibiting the initial rate of Na+, K+-pump fluxes in human and rat erythrocytes and in mouse macrophages respectively. 5. In conclusion, Na+, K+-pump fluxes measured under initial rate conditions in human erythrocytes exhibit an unusually high sensitivity to genins of cardiac glycosides. This property probably results from the fast binding rate constants of genins and the slow association rates of glycosides to human red cells.
authors.affiliation: INSERM U7, Hôpital Necker, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Senn
authors.forename: L G
authors.initials: LG
authors.lastname: Lelièvre
authors.forename: P
authors.initials: P
authors.lastname: Braquet
authors.forename: R
authors.initials: R
authors.lastname: Garay
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002298:Cardenolides / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood*
chemical_list: D002298:Cardenolides; D002301:Cardiac Glycosides; D010042:Ouabain; D012964:Sodium; D011188:Potassium