Inhibition of (Na/K)-ATPase by NFE induces an increase in mechanical activity of perfused guinea-pig heart.
The effect of 1-(5-nitro-2-furyl)-2-(phenylsulfonyl)-2-(furylcarbonyl)- ethylene (NFE) on stimulation of (Na/K)-ATPase by sodium and potassium ions was tested in isolated, partially purified sarcolemmal preparation from guinea-pig hearts. NFE inhibited competitively the stimulation of the enzyme by increasing concentrations of potassium. This inhibition was characterized by a significant (p < 0.001) increase of the K0.5 value, a considerable decrease of the Hill's cooperativity constant n as well as by an insignificant diminution of the Vmax value. Contrary to the effect on stimulation by potassium, NFE inhibited non-competitively the stimulation of the ATPase by sodium ions with a significant (p < 0.001) depression of Vmax but without any considerable effect on the K0.5 and n values. These results indicated that NFE may interact with the molecule of (Na/K)-ATPase in a locus close to or identical with the potassium binding site of the enzyme, i.e., in a similar mode as it was well documented for ouabain. This possibility was strongly supported by the finding that NFE administered at the concentration of 0.1 mumol/l in the perfusion medium increased significantly (p < 0.01) the mechanical activity of isolated perfused guinea-pig heart (Langendorff preparation). Nevertheless, it also caused some adverse effects such as a slight increase in coronary flow resistance and in heart rate as well as in the left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Vrbanová
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A
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava.
Stankovicová
T
T
Docolomanský
P
P
Stefko
I
I
Ziegelhöffer
A
A
Breier
A
A
D000818:Animals; D001665:Binding Sites; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D009581:Nitrofurans / Q000494:pharmacology*; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
C094416:1-(5-nitro-2-furyl)-2-(phenylsulfonyl)-2-(furylcarbonyl)ethylene; D009581:Nitrofurans; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium