Inhibitory effect of chloroquine on concanavalin A internalization into cell monolayer culture.

When cultured rat hepatoma cells (R-Y121B) were incubated with insulin in the presence of chloroquine at 25 degrees C, chloroquine increased both insulin binding to the cell surface and its internalization into cells. In addition, in order to elucidate whether or not the effect of chloroquine on insulin receptors is specific, concanavalin A binding to the cells was examined in the presence or absence of chloroquine, since insulin receptors have concanavalin A binding sites. When the cells were incubated with concanavalin A in the presence of chloroquine, this drug decreased concanavalin A internalization in a dose-dependent manner: The inhibitory effect of chloroquine on concanavalin A internalization was evident at a concentration as low as 0.05 mM, and increased up to 0.5 mM. The effect of chloroquine was not related to the degradation of concanavalin A incubated with cells. When the cells were incubated with concanavalin A at 4 degrees C in the presence of chloroquine even at 0.5 mM, the inhibitory effect of chloroquine was not observed. It is concluded that the behavior of insulin receptors in the presence of chloroquine is different from that of concanavalin A receptors, although insulin receptors have concanavalin A binding sites. Chloroquine apparently increases insulin binding to cells in vitro, and this is due to the effect of chloroquine on insulin-receptor recyclization to which lysosome contributes [16, 31, 32]; this drug inhibits the function of lysosome which digests insulin-receptor complexes and eventually insulin bound to its receptors is accumulated in intracellular compartments.(ABSTRACT TRUNCATED AT 250 WORDS)