Effects of f-actin stabilization or disassembly on epithelial cl-
secretion and na-k-2cl cotransport.
Matthews, Jeffrey B., Jeremy A. Smith, and Bruce J. Hrnjez.
Department of Surgery, Beth Israel Hospital, Harvard Medical
School, Boston MA
APStracts 3:0250C, 1996.
Previous studies showed that cAMP-dependent transepithelial Cl-
secretion of the intestinal cell line T84 is reduced by the F-actin
stabilizer phalloidin, an effect in part attributable to inhibition
of basolateral Na-K-2Cl cotransport. However, secretory responses are
preserved in cells treated with the microfilament disrupter
cytochalasin D. In the present study, we explore the effects of
cytochalasin D and two novel compounds derived from marine sponges on
the Cl- secretory apparatus of T84 cells. Jasplakinolide (which
stabilizes F-actin) inhibited cAMP-dependent secretion and Na-K-2Cl
cotransport. Latrunculin A (which sequesters G-actin monomers)
profoundly altered the distribution of F-actin and reduced basal
transepithelial resistance with minimal effect on secretion.
Cytochalasin D but not latrunculin A activated Na-K-2Cl cotransport.
The results provide further evidence that vectorial ion transport is
influenced by the cytoskeleton and support a model in which
disassembly of F-actin by specific pharmacologic means or in response
to secretory agonists favors activation of Na-K-2Cl cotransport.
Received 25 April 1996; accepted in final form 16 July 1996.
APS Manuscript Number C223-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996