Dual role for aluminum fluoride-sensitive g proteins in the
function of t84 epithelial cells: transport and barrier effects.
Ries, J[umlaut]urgen, J[umlaut]urgen Stein, Alexis E. Traynor-Kaplan,
and Kim E. Barrett.
Department of Medicine, University of California, San Diego, School
of Medicine, San Diego, California 92103
APStracts 3:0314C, 1996.
T84 monolayers were studied to determine the effect of AlF4-, an
activator of heterotrimeric G proteins, on chloride secretion and
intestinal barrier function. Basolateral (but not apical) addition of
AlF4- increased short-circuit current (Isc) and decreased
transepithelial resistance. Preincubation with the heavy metal
chelator, deferoxamine, showed that both effects were dependent on
aluminum. The effect on Isc was abolished by the intracellular Ca2+
-chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
(BAPTA) or in chloride-free solutions, while the decrease in
resistance was unaffected. AlF4- also increased intracellular
calcium, as assessed via Fura-2 fluorimetry. AlF4- had no effect on
cAMP or cGMP levels in T84 cells. The effect of AlF4- on
transepithelial resistance was accompanied by a decrease in cellular
F-actin as well as increased transepithelial fluxes of the
paracellular markers mannitol and inulin. The results indicate that
AlF4- - sensitive G proteins regulate both epithelial secretory and
barrier function, but via different pathways. AlF4- increases
chloride secretion via a calcium-dependent and cAMP- and cGMP
-independent mechanism in T84 cells, while the decrease in resistance
is independent of calcium.
Received 13 March 1996; accepted in final form 18 September 1996.
APS Manuscript Number C145-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996