Epidermal growth factor inhibits calcium-dependent chloride ion
transport in t84 human colonic epithelial cells.
Uribe, Jorge M., Cornelia M. Gelbmann, Alexis E. Traynor-Kaplan, and
Kim E. Barrett.
Department of Medicine, University of California, San Diego, School
of Medicine, San Diego, California 92103
APStracts 3:0115C, 1996.
This study examined whether epidermal growth factor (EGF) inhibits
calcium-dependent chloride secretion by T84 cells. Basolateral EGF
inhibited chloride secretion induced by carbachol or thapsigargin,
without blocking the rise in intracellular calcium. Studies have
shown that carbachol renders T84 cells refractory to subsequent
stimulation by thapsigargin, an effect ascribed to D-myo-inositol
(3,4,5,6) tetrakisphosphate (D-Ins(3,4,5,6)P4). EGF also increased
DL-Ins(3,4,5,6)P4 to a maximum of 170% above control. However,
despite the fact that EGF inhibited chloride secretion at 1 minute,
DL-Ins(3,4,5,6)P4 was not elevated at this timepoint. EGF plus
carbachol had a greater inhibitory effect on chloride secretion than
either alone, indicating the likely involvement of an additional
inhibitory pathway activated by EGF. Staurosporine did not alter
EGF's ability to inhibit chloride secretion or increase DL
-Ins(3,4,5,6)P4. In contrast, genistein inhibited the rise in DL
-Ins(3,4,5,6)P4 and partially reversed inhibition of effect on
chloride secretion. In conclusion, EGF and carbachol can both inhibit
chloride secretion via D-Ins(3,4,5,6)P4, while EGF also generates an
additional inhibitory signal.
Received 18 January 1995; accepted in final form 26 March 1996.
APS Manuscript Number C29-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96