The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase
Апстракт
The in vitro influence of potassium ion modulations, in the concentration range 2mM - 500mM, on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase activity was studied. The response of enzymatic activity in the presence of various K+ concentrations to digoxin was biphasic, thereby, indicating the existence of two Na+/K+-ATPase isoforms, differing in the affinity towards the tested drug. Both isoforms showed higher sensitivity to digoxin in the presence of K+ ions below 20mM in the medium assay. The IC50 values for high/low isoforms 2.77 x 10(-6) M/8.56 x 10(-5) Mand 7.06 x 10(-7) M/1.87 x 10(-5) Mwere obtained in the presence of optimal (20mM) and 2mMK(+), respectively. However, preincubation in the presence of elevated K+ concentration (50 - 500mM) in the medium assay prior to Na+/K+-ATPase exposure to digoxin did not prevent the inhibition, i.e. IC50 values for both isoforms was the same as in the presence of the optimal K+ concentration. On the contrary, addition of... 200mMK(+) into the medium assay after 10 minutes exposure of Na+/K+-ATPase to digoxin, showed a time-dependent recovery effect on the inhibited enzymatic activity. Kinetic analysis showed that digoxin inhibited Na+/K+-ATPase by reducing maximum enzymatic velocity (V-max) and K-m, implying an uncompetitive mode of interaction.
Кључне речи:
Na+/K+-ATPase / digoxin / inhibition / potassium modulationsИзвор:
Journal of Enzyme Inhibition and Medicinal Chemistry, 2006, 21, 4, 471-475
DOI: 10.1080/14756360600642230
ISSN: 1475-6366
PubMed: 17059183
WoS: 000240322000019
Scopus: 2-s2.0-33748484061
Колекције
Институција/група
VinčaTY - JOUR AU - Krstić, Danijela Z. AU - Tomić, Nenad AU - Krinulović, Katarina AU - Vasić, Vesna M. PY - 2006 UR - https://vinar.vin.bg.ac.rs/handle/123456789/3081 AB - The in vitro influence of potassium ion modulations, in the concentration range 2mM - 500mM, on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase activity was studied. The response of enzymatic activity in the presence of various K+ concentrations to digoxin was biphasic, thereby, indicating the existence of two Na+/K+-ATPase isoforms, differing in the affinity towards the tested drug. Both isoforms showed higher sensitivity to digoxin in the presence of K+ ions below 20mM in the medium assay. The IC50 values for high/low isoforms 2.77 x 10(-6) M/8.56 x 10(-5) Mand 7.06 x 10(-7) M/1.87 x 10(-5) Mwere obtained in the presence of optimal (20mM) and 2mMK(+), respectively. However, preincubation in the presence of elevated K+ concentration (50 - 500mM) in the medium assay prior to Na+/K+-ATPase exposure to digoxin did not prevent the inhibition, i.e. IC50 values for both isoforms was the same as in the presence of the optimal K+ concentration. On the contrary, addition of 200mMK(+) into the medium assay after 10 minutes exposure of Na+/K+-ATPase to digoxin, showed a time-dependent recovery effect on the inhibited enzymatic activity. Kinetic analysis showed that digoxin inhibited Na+/K+-ATPase by reducing maximum enzymatic velocity (V-max) and K-m, implying an uncompetitive mode of interaction. T2 - Journal of Enzyme Inhibition and Medicinal Chemistry T1 - The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase VL - 21 IS - 4 SP - 471 EP - 475 DO - 10.1080/14756360600642230 ER -
@article{ author = "Krstić, Danijela Z. and Tomić, Nenad and Krinulović, Katarina and Vasić, Vesna M.", year = "2006", abstract = "The in vitro influence of potassium ion modulations, in the concentration range 2mM - 500mM, on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase activity was studied. The response of enzymatic activity in the presence of various K+ concentrations to digoxin was biphasic, thereby, indicating the existence of two Na+/K+-ATPase isoforms, differing in the affinity towards the tested drug. Both isoforms showed higher sensitivity to digoxin in the presence of K+ ions below 20mM in the medium assay. The IC50 values for high/low isoforms 2.77 x 10(-6) M/8.56 x 10(-5) Mand 7.06 x 10(-7) M/1.87 x 10(-5) Mwere obtained in the presence of optimal (20mM) and 2mMK(+), respectively. However, preincubation in the presence of elevated K+ concentration (50 - 500mM) in the medium assay prior to Na+/K+-ATPase exposure to digoxin did not prevent the inhibition, i.e. IC50 values for both isoforms was the same as in the presence of the optimal K+ concentration. On the contrary, addition of 200mMK(+) into the medium assay after 10 minutes exposure of Na+/K+-ATPase to digoxin, showed a time-dependent recovery effect on the inhibited enzymatic activity. Kinetic analysis showed that digoxin inhibited Na+/K+-ATPase by reducing maximum enzymatic velocity (V-max) and K-m, implying an uncompetitive mode of interaction.", journal = "Journal of Enzyme Inhibition and Medicinal Chemistry", title = "The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase", volume = "21", number = "4", pages = "471-475", doi = "10.1080/14756360600642230" }
Krstić, D. Z., Tomić, N., Krinulović, K.,& Vasić, V. M.. (2006). The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase. in Journal of Enzyme Inhibition and Medicinal Chemistry, 21(4), 471-475. https://doi.org/10.1080/14756360600642230
Krstić DZ, Tomić N, Krinulović K, Vasić VM. The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2006;21(4):471-475. doi:10.1080/14756360600642230 .
Krstić, Danijela Z., Tomić, Nenad, Krinulović, Katarina, Vasić, Vesna M., "The influence of potassium ion (K+) on digoxin-induced inhibition of porcine cerebral cortex Na+/K+-ATPase" in Journal of Enzyme Inhibition and Medicinal Chemistry, 21, no. 4 (2006):471-475, https://doi.org/10.1080/14756360600642230 . .