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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
Author(s) -
GHYSELBURTON JOSIANE,
GODFRAIND T.
Publication year - 1979
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1979.tb13662.x
Subject(s) - ouabain , contractility , inotrope , ed50 , chemistry , stimulation , guinea pig , endocrinology , medicine , sodium , sodium pump , biophysics , biology , biochemistry , receptor , organic chemistry
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 Na i whereas high doses produced an increase. Dihydroouabain evoked only a Na i gain. 3 The increase of KCl concentration from 2.7 to 12 m m decreased Na i in untreated atria and displaced ouabain dose‐effect curves to the right. 4 ED 50 values for the positive inotropic effect were lower than ED 50 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.