AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 5 818-G822, Copyright © 1989 by American Physiological Society
Effects of quinacrine on calcium active transport by rat intestinal epithelium
M. J. Favus, V. Tembe, M. D. Tanklefsky, K. A. Ambrosic and H. N. Nellans
Department of Medicine, University of Chicago, Illinois 60637.
To determine the possible role of acidic lysosomal vesicles in the
transcellular transport of Ca, bidirectional Ca fluxes were measured across
intestinal segments in vitro in the absence of electrochemical gradients.
Mucosal addition of the weak base quinacrine (0.2 mM) caused a 67% decline
in the mucosal-to-serosal Ca flux (Jm----s) across duodenum (175 +/- 34 vs.
58 +/- 9 nmol.cm-2.h-1, P less than 0.007) and reduced cecal Ca Jm----s
(177 +/- 15 vs. 45 +/- 4, P less than 0.0001). Higher concentrations of up
to 2.0 mM caused no further decline in cecal Ca Jm----s. Inhibition of
cecal Ca Jm----s by mucosal chloroquine (0.1 mM) or ammonium chloride (10
mM) varied from 37 to 50%. Addition in vitro of quinacrine to enterocyte
basolateral membrane vesicles failed to inhibit ATP-dependent Ca uptake.
The present studies demonstrate that agents that collapse lysosomal pH
gradients inhibit transcellular Ca transport. These observations are
consistent with the hypothesis that Ca destined for transcellular transport
is functionally associated with acidic lysosomes and that these organelles
play an important role in transepithelial Ca translocation.
