Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase
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Аутори
Krstić, Danijela Z.![](/themes/MirageVinar/images/orcid.png)
Krinulović, Katarina
Spasojević-Tišma, Vera D.
Joksić, Gordana
![](/themes/MirageVinar/images/orcid.png)
Momić, Tatjana
![](/themes/MirageVinar/images/orcid.png)
Vasić, Vesna M.
![](/themes/MirageVinar/images/orcid.png)
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Inhibition of Na+/K+-ATPase activity from human erythrocyte membranes and commercial porcine cerebral cortex by in vitro single and simultaneous exposure to digoxin and gitoxin was investigated to elucidate the difference in the mechanism of the enzyme inhibition by structurally different cardiac glycosides. The drugs exerted a biphasic dose-dependent inhibitory effect on the enzyme activity in both tissues, supporting the existence of two sensitive Na+/K+-ATPase isoforms. The IC50 values for the low and high affinity isoforms were calculated from the inhibition curves using mathematical analysis. The Hill coefficient (n) fulfilled the relationship 1 LT n LT 3; suggesting cooperative binding of inhibitors to the enzyme. Kinetic analysis showed that digoxin and gitoxin inhibited Na+/K+-ATPase by reducing the maximum enzymatic velocity (V-max) and K-m, implying an uncompetitive mode of interaction. Both the isoforms were always more sensitive to gitoxin. The erythrocyte enzyme was more s...ensitive to the inhibitors in the range of low concentrations but the commercial cerebral cortex enzyme exerted a higher sensitivity in high inhibitors affinity concentration range. By simultaneous exposure of the enzyme to digoxin and gitoxin in combinations a synergistic effect was achieved by low inhibitor concentrations. An antagonistic effect was obtained with erythrocyte membrane enzyme at high inhibitors concentration.
Кључне речи:
digoxin / gitoxin / Na+/K+-ATPase / erythrocytes / porcine cerebral cortex / inhibition / kineticsИзвор:
Journal of Enzyme Inhibition and Medicinal Chemistry, 2004, 19, 5, 409-415
DOI: 10.1080/14756360410001722065
ISSN: 1475-6366; 1475-6374
PubMed: 15648655
WoS: 000225878100004
Scopus: 2-s2.0-11044223220
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Институција/група
VinčaTY - JOUR AU - Krstić, Danijela Z. AU - Krinulović, Katarina AU - Spasojević-Tišma, Vera D. AU - Joksić, Gordana AU - Momić, Tatjana AU - Vasić, Vesna M. PY - 2004 UR - https://vinar.vin.bg.ac.rs/handle/123456789/2838 AB - Inhibition of Na+/K+-ATPase activity from human erythrocyte membranes and commercial porcine cerebral cortex by in vitro single and simultaneous exposure to digoxin and gitoxin was investigated to elucidate the difference in the mechanism of the enzyme inhibition by structurally different cardiac glycosides. The drugs exerted a biphasic dose-dependent inhibitory effect on the enzyme activity in both tissues, supporting the existence of two sensitive Na+/K+-ATPase isoforms. The IC50 values for the low and high affinity isoforms were calculated from the inhibition curves using mathematical analysis. The Hill coefficient (n) fulfilled the relationship 1 LT n LT 3; suggesting cooperative binding of inhibitors to the enzyme. Kinetic analysis showed that digoxin and gitoxin inhibited Na+/K+-ATPase by reducing the maximum enzymatic velocity (V-max) and K-m, implying an uncompetitive mode of interaction. Both the isoforms were always more sensitive to gitoxin. The erythrocyte enzyme was more sensitive to the inhibitors in the range of low concentrations but the commercial cerebral cortex enzyme exerted a higher sensitivity in high inhibitors affinity concentration range. By simultaneous exposure of the enzyme to digoxin and gitoxin in combinations a synergistic effect was achieved by low inhibitor concentrations. An antagonistic effect was obtained with erythrocyte membrane enzyme at high inhibitors concentration. T2 - Journal of Enzyme Inhibition and Medicinal Chemistry T1 - Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase VL - 19 IS - 5 SP - 409 EP - 415 DO - 10.1080/14756360410001722065 ER -
@article{ author = "Krstić, Danijela Z. and Krinulović, Katarina and Spasojević-Tišma, Vera D. and Joksić, Gordana and Momić, Tatjana and Vasić, Vesna M.", year = "2004", abstract = "Inhibition of Na+/K+-ATPase activity from human erythrocyte membranes and commercial porcine cerebral cortex by in vitro single and simultaneous exposure to digoxin and gitoxin was investigated to elucidate the difference in the mechanism of the enzyme inhibition by structurally different cardiac glycosides. The drugs exerted a biphasic dose-dependent inhibitory effect on the enzyme activity in both tissues, supporting the existence of two sensitive Na+/K+-ATPase isoforms. The IC50 values for the low and high affinity isoforms were calculated from the inhibition curves using mathematical analysis. The Hill coefficient (n) fulfilled the relationship 1 LT n LT 3; suggesting cooperative binding of inhibitors to the enzyme. Kinetic analysis showed that digoxin and gitoxin inhibited Na+/K+-ATPase by reducing the maximum enzymatic velocity (V-max) and K-m, implying an uncompetitive mode of interaction. Both the isoforms were always more sensitive to gitoxin. The erythrocyte enzyme was more sensitive to the inhibitors in the range of low concentrations but the commercial cerebral cortex enzyme exerted a higher sensitivity in high inhibitors affinity concentration range. By simultaneous exposure of the enzyme to digoxin and gitoxin in combinations a synergistic effect was achieved by low inhibitor concentrations. An antagonistic effect was obtained with erythrocyte membrane enzyme at high inhibitors concentration.", journal = "Journal of Enzyme Inhibition and Medicinal Chemistry", title = "Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase", volume = "19", number = "5", pages = "409-415", doi = "10.1080/14756360410001722065" }
Krstić, D. Z., Krinulović, K., Spasojević-Tišma, V. D., Joksić, G., Momić, T.,& Vasić, V. M.. (2004). Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase. in Journal of Enzyme Inhibition and Medicinal Chemistry, 19(5), 409-415. https://doi.org/10.1080/14756360410001722065
Krstić DZ, Krinulović K, Spasojević-Tišma VD, Joksić G, Momić T, Vasić VM. Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2004;19(5):409-415. doi:10.1080/14756360410001722065 .
Krstić, Danijela Z., Krinulović, Katarina, Spasojević-Tišma, Vera D., Joksić, Gordana, Momić, Tatjana, Vasić, Vesna M., "Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase" in Journal of Enzyme Inhibition and Medicinal Chemistry, 19, no. 5 (2004):409-415, https://doi.org/10.1080/14756360410001722065 . .