AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 3 439-G444, Copyright © 1992 by American Physiological Society
Effects of chloroquine and methylamine on lysosomal enzyme secretion by rat pancreas
T. Hirano, A. Saluja, P. Ramarao, M. M. Lerch and M. L. Steer
Department of Surgery, Harvard Medical School, Boston, Massachusetts.
In vivo pancreatic secretion of the lysosomal hydrolase cathepsin B was
found to be increased by infusion of the secretagogue caerulein. The basal
as well as caerulein-stimulated in vivo rate of cathepsin B was further
increased by infusion of either chloroquine or methylamine while neither
the basal nor the secretagogue-stimulated rates of amylase secretion were
altered by the lysosomotropic agents. These observations indicate that
neutralization of the acidic prelysosomal compartment by administration of
lysosomotropic agents results in lysosomal enzyme entry, by default, into
the regulated secretory pathway. In vitro stimulation of pancreatic acini
with caerulein was also found to stimulate cathepsin B secretion. That in
vitro rate of cathepsin B secretion stimulated by caerulein was not
increased in acini prepared from animals infused with caerulein,
chloroquine, or methylamine, but the in vitro rate of cathepsin B secretion
stimulated by caerulein was increased in acini prepared from animals
infused with caerulein plus either chloroquine or methylamine. Under these
conditions, redistribution of cathepsin B from the lysosome-enriched to the
zymogen granule-enriched subcellular fraction was noted, and lysosomal
enzyme-containing organelles became increasingly fragile. These
observations indicate that in vivo secretagogue stimulation increases the
degree of diversion of lysosomal hydrolases into the regulated secretory
compartment when the prelysosomal compartment has been neutralized with
lysosomotropic agents.
