Effects of local anaesthetics on the activity of the Na,K-ATPase of canine renal medulla.

Abstract The purpose of this study is to characterize the effects of local anaesthetics on Na,K-ATPase activity. The ATPase activity of Na,K-ATPase-enriched membranes from canine renal medulla was determined in the absence and in the presence of lidocaine, procaine, tetracaine, benzocaine, bupivacaine, prilocaine, and procainamide at 37 and 25°C. All of these local anaesthetics, except benzocaine, inhibit the activity of the Na,K-ATPase of canine renal medulla at both 25 and 37°C. Benzocaine inhibits Na,K-ATPase activity at 37°C, but stimulates activity at 25°C. The influence of lidocaine on stimulation of Na,K-ATPase activity by Na + and K + was investigated. Lidocaine increases the apparent K 0.5 of the Na,K-ATPase for both Na + and K + and decreases the V max values for both ions. IC 50 values for lidocaine increase with increasing concentrations of both Na + and K + . The data indicate that lidocaine diminishes the affinity of the Na,K-ATPase for Na + and K + and that binding of Na + or K + decreases the potency of lidocaine as an inhibitor of the Na,K-ATPase. Lidocaine markedly decreases the affinity of the Na,K-ATPase for ouabain, but only slightly diminishes the maximum amount of ouabain bound. Unprotonated lidocaine is apparently a more potent inhibitor than is the protonated form. 2000 Academic Press@p$hr