Tannin inhibits adenylate cyclase in airway epithelial cells.
Cloutier, Michelle M., M. D., Linda Guernsey.
Pediatric Pulmonary Division, University of Connecticut Health
Center, Farmington, Connecticut 06030
APStracts 2:0014L, 1995.
Tannin, isolated from cotton bracts extract and implicated in the
pathogenesis of byssinosis, inhibits cAMP production and chloride
secretion in bovine airway epithelial cells in part by inhibiting
adrenergic receptor binding. The purpose of this study was to
determine whether tannin affected other parts of the adrenergic-cAMP
signal transduction pathway by examining the effect of tannin on GTP
-regulatory pathways (G proteins) and on adenylate cyclase activity.
cAMP production in confluent airway epithelial cells was measured in
the presence of cholera toxin (100 [mu]g/ml), an activator of Gs
proteins, and forskolin (0.1 - 1000 [mu]M), a direct activator of
adenylate cyclase. Cholera toxin stimulated cAMP production; this
response, however, was inhibited in cells pretreated with 50 [mu]g/ml
tannin. Forskolin (100 [mu]M) stimulated cAMP production 13-fold above
baseline values. Tannin pretreatment inhibited the stimulatory effect
of forskolin on cAMP release in a dose-dependent manner with an IC50
(tannin concentration causing 50% inhibition) of 7.5 [mu]g/ml. The
stimulatory effect of forskolin on cAMP release was completely
inhibited in cells pretreated with 50 [mu]g/ml tannin. The inhibition
was reversible 3 h after removal of tannin from the solution. Tannin
also inhibited forskolin-stimulated adenylate cyclase activity in a
dose-dependent, non-competitive manner. We conclude that forskolin
and cholera toxin stimulate cAMP production in airway epithelial
cells and that tannin inhibits the production of cAMP in airway
epithelial cells by a direct effect upon adenylate cyclase activity.
Received 17 August 1994; accepted in final form 22 December 1994.
APS Manuscript Number L239-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.