Mechanisms of cellular enzyme release. I. Alteration in membrane fluidity and permeability.

Above-normal plasma enzyme activities resulting from increased release of intracellular macromolecules are an important diagnostic feature of Duchenne muscular dystrophy. These and other biochemical and histological characteristics of this disease are faithfully duplicated when imipramine and serotonin are administered to the rat. Imipramine, but not serotonin alone, causes release of enzymes from rat diaphragms and human lymphocytes and release of hemoglobin from erythrocytes in vitro. Ouabain causes neither. Imipramine-induced enzyme release is decreased by adding ATP to the specimen in vitro or in hypertonic solution. Imipramine inhibits the capping phenomenon (an aggregation of antigen/antibody complexes of the membrane) of human B lymphocytes labeled with fluorescein-conjugated antihuman immunoglobulins. Serotonin alone has no such effect, but, administered together with imipramine, it potentiates the inhibition of capping by imipramine.