Almotrefi A A, Dzimiri N
Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.
Pharmacol Toxicol. 1991 Aug;69(2):140-3. doi: 10.1111/j.1600-0773.1991.tb01287.x.
The effects of varying incubation K+ concentration on the inhibitory action of amiodarone on the Mg(2+)-dependent ATP hydrolysis by myocardial Na(+)-K(+)-ATPase (EC 3.6.1.3) were studied in guinea pig heart preparations. In the first part of the study, it was established that the activity of the enzyme increased with growing concentrations up to approximately 20 mM K+. The concentration-response relationships for amiodarone were investigated in incubation media containing 2.5, 5.0 and 10 mM K+ respectively. Amiodarone exhibited similar concentration-dependent inhibitory effects in the range of 0.01 nM-80 microM at 2.5 mM, 0.13-150 microM at 5.0 mM and 0.3-700 microM at 10.0 mM K+. The corresponding IC50 values were 10.4 +/- 3.2 microM, 28.3 +/- 7.6 microM at 5.0 mM and 33.3 +/- 9.2 microM at 10.0 mM K+, respectively. Thus, reduction in the K+ concentration from the "standard" 5.0 to 2.5 mM was accompanied by a significant right-to-left shift in the inhibitory potency of amiodarone, the effective concentrations being shifted from microM into nM ranges. Increasing K+ concentration to 10 mM on the other hand attained opposite but less remarkable effects. The results show that the in vitro inhibition of myocardial Na(+)-K(+)-ATPase activity by amiodarone is related to the K+ concentration of the incubation medium. These effects may be pertinent to the mechanism by which this drug interferes with the electrogenic Na+/K+ pump activity of the enzyme, thereby probably contributing to the mechanism(s) responsible for some of its cardiac actions.
在豚鼠心脏制剂中研究了不同孵育钾离子浓度对胺碘酮抑制心肌钠钾ATP酶（EC 3.6.1.3）镁依赖的ATP水解作用的影响。在研究的第一部分，确定了酶活性随着钾离子浓度增加至约20 mM而升高。分别在含2.5、5.0和10 mM钾离子的孵育介质中研究了胺碘酮的浓度-反应关系。在2.5 mM钾离子时，胺碘酮在0.01 nM - 80 μM范围内表现出相似的浓度依赖性抑制作用；在5.0 mM钾离子时，为0.13 - 150 μM；在10.0 mM钾离子时，为0.3 - 700 μM。相应的IC50值分别为10.4 ± 3.2 μM、5.0 mM时为28.3 ± 7.6 μM和10.0 mM钾离子时为33.3 ± 9.2 μM。因此，将钾离子浓度从“标准”的5.0 mM降至2.5 mM伴随着胺碘酮抑制效力的显著右移至左移，有效浓度从μM范围移至nM范围。另一方面，将钾离子浓度增加至10 mM则产生相反但不太显著的效果。结果表明，胺碘酮对心肌钠钾ATP酶活性的体外抑制作用与孵育介质中的钾离子浓度有关。这些效应可能与该药物干扰酶的电生性钠/钾泵活性的机制相关，从而可能有助于解释其某些心脏作用的机制。
