Clinical Chemistry, Vol 23, 2226-2230, Copyright © 1977 by American Association for Clinical Chemistry

Mechanisms of cellular enzyme release. II. Inhibition of sarcolemmal enzymes by myopathy-inducing agents

HL Verrill, HD Gruemer and N Baba

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.