The lysosomotropic agent chloroquine is widely used as a specific inhibitor of intralysosomal proteolysis in isolated hepatocytes. It was shown that in vitro chloroquine reversibly inhibited purified cathepsins H, B, L in concentrations less than those observed inside lysosomes in vivo. However, administration of high doses of chloroquine to rats (30 -50 mg/kg i.p. as a single or repeated injections) was followed by increased cathepsin D and cysteine proteinase activities, as well as other lysosomal enzymes. Chloroquine administration did not induce any changes of carbon particles phagocytosis by liver cells (macrophages); modifications of fluid-phase ( 125 I-PVP uptake) and receptor-mediated endocytosis ( 125 I-asialo-fetuin uptake) were noted. Chloroquine administered in vivo reproduced some symptoms of lysosomal storage diseases (especially during repeated drug administration).

In order to gain knowledge on the interaction of lysosomes with proteins, we have assessed the equilibrium densities of the lysosomal membrane and matrix markers after in vitro incubation of rat liver lysosomes with various polypeptides. The addition of basic polypeptides, polylysine or protamine, to the suspension of lysosomes brought about a profound alteration of lysosomal membrane, causing extensive leakage of lysosomal matrix enzymes. Electron microscopic observation revealed a remarkable aggregation of lysosomes by the basic polypeptides. Polyglutamic acid, an acidic polypeptide, did not produce such effect. ATP was found to stabilize lysosomes during incubation, particularly with basic polypeptides.