Stimulation and inhibition of the sodium pump by cardioactive steroids in relation to their binding sites and their inotropic effect on guinea-pig isolated atria.
1 The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea-pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined. 2 The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Nai whereas high doses produced an increase. Dihydroouabain evoked only a Nai gain. 3 The increase of KCl concentration from 2.7 to 12 mM decreased Nai in untreated atria and displaced ouabain dose-effect curves to the right. 4 ED50 values for the positive inotropic effect were lower than ED50 values for the inhibition of the pump and were not similarly affected by an increase in KCl concentration. 5 The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively. 6 The increase in KCl reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high-affinity sites whereas the capacity of the other sites remained unchanged. 7 The results confirm the existence of two specific binding sites for ouabain in guinea-pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.
D000818:Animals; D016275:Atrial Function; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D010042:Ouabain; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002118:Calcium