Effects of local anaesthetics on the activity of the Na,K-ATPase of canine renal medulla.
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 degrees 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 degrees C. Benzocaine inhibits Na,K-ATPase activity at 37 degrees C, but stimulates activity at 25 degrees 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.
Kutchai
H
H
Department of Molecular Physiology and Biological Physics, School of Medicine, University of Virginia, Charlottesville, VA 22906, USA.
Geddis
L M
LM
Farley
R A
RA
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D007679:Kidney Medulla / Q000201:enzymology*; D008012:Lidocaine / Q000494:pharmacology; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D012995:Solubility
D000779:Anesthetics, Local; D010042:Ouabain; D008012:Lidocaine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium