DISSOCIATION OF CONTRACTILE EFFECT AND BINDING AND INHIBITION OF Na⁺-K⁺-ADENOSINE TRIPHOSPHATASE BY CARDIAC GLYCOSIDES IN RABBIT MYOMETRIUM

¹ Department of Pharmacology, The University of Alberta, Edmonton, Alberta, Canada

Studies on the action of ouabain and digitoxin on contractile function of rabbit myometrium showed that both the glycosides (5 x 10^-7 M) potentiated acetylcholine-induced contractions within 10 minutes and this action disappeared on washing with drug-free normal Krebs-Ringer solution within 10 minutes. The binding of ³H-ouabain (5 x 10^-7 M) to plasma membrane fraction, however, did not wash off completely in 10 minutes (only 23% of total ouabain bound was released) and also this binding was not decreased by 23 mM K⁺ in 10 minutes, though K⁺-free Krebs-Ringer solution increased the binding in 10 minutes. Thus, the contractile effect of ouabain occurring after 10 minutes in normal Krebs-Ringer solution may not be related to the binding of these drugs to Na⁺-K⁺-adenosine triphosphatase (ATPase). Studies on the effect of ouabain and digitoxin on ion recovery of Na⁺-rich tissues showed that 5 x 10^-7 M ouabain or digitoxin did not inhibit ion recovery in 10 minutes. Even 10^-5 M ouabain or digitoxin did not inhibit ion recovery in 10 minutes. On 30 minutes exposure, all the concentrations inhibited ion recovery (30% with 5 x 10^-7 or 10^-6 M and 50% with 10^-5 M compared to controls). These results suggest that inhibition of Na⁺-K⁺-ATPase is not the mechanism of potentiation of contractile effect as these two effects could be dissociated.

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