ACTIONS OF AMIODARONE ON MITOCHONDRIAL ATPASE AND LACTATE-DEHYDROGENASE ACTIVITIES IN GUINEA-PIG HEART PREPARATIONS

The effects of amiodarone on mitochondrial ATPase (EC 3.6.1.3) and lac tate dehydrogenase (LDH: EC 1.1.1.27) activities were studied in guine a pig mitochondrial preparations in order to test the hypothesis that amiodarone exerts some of its effects as a result of multiple actions on membrane-bound enzymes and receptors. Amiodarone inhibited the ATPa se activity in the range of 10 pM to 10 mM (n = 10) with IC50 values o f 56.4 +/- 7.2 muM. However, although the inhibitory action was very s ignificant (P < 0.0001, compared to the control) in the concentration range of 100 pM to 10 muM, the differences in individual enzyme respon ses showed very weak correlation with drug concentration. In this regi on, the inhibitory effects were almost constant at approximately 37%. Below 100 pM and above this range however, the concentration-response relationships were steep, reaching total inhibition at approximately 2 .5 mM. Amiodarone also exerted concentration-dependent inhibitory effe cts on lactate dehydrogenase activity. However, over the effective inh ibitory concentration range (5-95%) of 7.5 muM to 2.5 mM (n = 8) and I C50 value of 108 +/- 6 muM, its inhibitory potency was twofold weaker than that of its ATPase inhibition. We propose that these actions cont ribute, at least in part, to the mechanism(s) of some of the pharmacol ogical actions of amiodarone.