Interaction between monensin and lysosomotropic amines in the regulation of the processing of epidermal growth factor by BALB/c 3T3 cells

Monensin, like the lysosomotropic amines Chloroquine and methylamine, caused a large accumulation of ¹²⁵I-EGF in BALB/c-3T3 cells that was due to specific increases in the amount of intracellular intact hormone. However using a pulse-chase paradigm of ¹²⁵I-EGF accumulation, marked differences were observed between monensin and the amines. When EGF was accumulated in the presence of monensin, there was a gradual loss of cell-bound radioactivity during a chase in the absence of the drug, and the labeled material recovered in. the medium primarily consisted of degraded hormone. The continued presence of monensin in the chase medium substantively prevented the loss of cell bound material, and what little was recovered in the medium consisted of intact ¹²⁵I-EGF. In contrast, when ¹²⁵I-EGF was accumulated in the presence of methylamine, predominately intact peptide was lost from the cells at a relatively high rate during the chase whether or not methylamine remained in the medium. When monensin was present in the chase medium following accumulation in the presence of either Chloroquine or methylamine, the loss of intracellular ¹²⁵I-EGF was essentially blocked.