Mechanisms of cellular enzyme release. II. Inhibition of sarcolemmal enzymes by myopathy-inducing agents.
A defective membrane mechanism has been suggested [Arch. Neurol. 33, 315 (1976)] for the pathogenesis of Duchenne muscular dystrophy. The characteristic clinical and biological findings, including leakage of cellular enzymes into the serum in the disease, have been duplicated by the imipramine/serotonin rat myopathy model. Sarcolemma was prepared from quadriceps femoris muscles of control and myopathy-affected animals. The activities of sarcolemmal adenosinetriphosphatase and acetylcholinesterase were inhibited in vitro by imipramine and serotonin. The inhibition by imipramine of these sarcolemma-bound enzyme systems decreased the Vmax and increased the Km. This mixed type of inhibition is consistent with an imipramine-induced interference at these enzyme sites and a disruption of lipid-protein interrelations. We hypothesize that such conformational membrane changes might contribute to the leakage of macromolecules such as enzymes from the cell interior.
D000110:Acetylcholinesterase / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D009137:Muscular Dystrophy, Animal / Q000201:enzymology*; D051381:Rats; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D012701:Serotonin / Q000494:pharmacology*
D012701:Serotonin; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; D007099:Imipramine