AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 5 851-L855, Copyright © 1995 by American Physiological Society
Tannin inhibits adenylate cyclase in airway epithelial cells
M. M. Cloutier and L. Guernsey
Pediatric Pulmonary Division, University of Connecticut Health Center, Farmington 06030, USA.
Tannin, isolated from cotton bracts extract and implicated in the
pathogenesis of byssinosis, inhibits adenosine 3',5'-cyclic monophosphate
(cAMP) production and Cl- 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 guanosine
5'-triphosphate (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 micrograms/ml), an activator
of GS proteins, and forskolin (0.1-1,000 microM), a direct activator of
adenylate cyclase. Cholera toxin stimulated cAMP production; this response,
however, was inhibited in cells pretreated with 50 micrograms/ml tannin.
Forskolin (100 microM) 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 a tannin concentration
causing 50% inhibition of 7.5 micrograms/ml. The stimulatory effect of
forskolin on cAMP release was completely inhibited in cells pretreated with
50 micrograms/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, noncompetitive 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 on adenylate cyclase activity.
