Acetylcholinesterase: a probe for the study of antiarrhythmic drug-membrane interactions.
Structural consequences of antiarrhythmic drug interaction with erythrocyte membranes were analyzed in terms of resulting changes in the activity of membrane-associated acetylcholinesterase. When enzyme inhibitory effects of drugs were compared at concentrations producing an equivalent degree of erythrocyte antihemolysis, a number of distinct groupings emerged, indicating that the molecular consequences of drug-membrane interaction are not identical for all agents examined. Differences in drug-induced acetylcholinesterase inhibition in intact erythrocytes, erythrocyte membranes and a brain synaptic membrane preparation emphaized the role of membrane structural organization in determining the functional consequences of antiarrhythmic interaction in any given system. While the inhibitory actions of lidocaine, D-600 and bretylium in intact red cells were not altered by an increased transmembrane chloride gradient, enhanced enzyme inhibition by quinidine and propranolol was observed under these conditions. The diverse perturbational actions of these membrane-stabilizing antiarrhythmics observed here may be indicative of a corresponding degree of complexity in the mechanisms whereby substances modify the potential-dependent properties of excitable tissues.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D013570:Synaptic Membranes / Q000201:enzymology
D000889:Anti-Arrhythmia Agents; D000110:Acetylcholinesterase