PMID- 7762688 OWN - NLM STAT- MEDLINE DCOM- 19950629 LR - 20171213 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 268 IP - 5 Pt 1 DP - 1995 May TI - Tannin inhibits adenylate cyclase in airway epithelial cells. PG - L851-5 AB - 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. FAU - Cloutier, M M AU - Cloutier MM AD - Pediatric Pulmonary Division, University of Connecticut Health Center, Farmington 06030, USA. FAU - Guernsey, L AU - Guernsey L LA - eng GR - HL-28669/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Adenylyl Cyclase Inhibitors) RN - 0 (Hydrolyzable Tannins) RN - 1F7A44V6OU (Colforsin) RN - 9012-63-9 (Cholera Toxin) RN - E0399OZS9N (Cyclic AMP) RN - EC 4.6.1.1 (Adenylyl Cyclases) SB - IM MH - *Adenylyl Cyclase Inhibitors MH - Adenylyl Cyclases/metabolism MH - Animals MH - Cattle MH - Cells, Cultured MH - Cholera Toxin/pharmacology MH - Colforsin/pharmacology MH - Cyclic AMP/metabolism MH - Dose-Response Relationship, Drug MH - Hydrolyzable Tannins/*pharmacology MH - Intracellular Membranes/metabolism MH - Trachea/cytology/*enzymology EDAT- 1995/05/01 00:00 MHDA- 1995/05/01 00:01 CRDT- 1995/05/01 00:00 PHST- 1995/05/01 00:00 [pubmed] PHST- 1995/05/01 00:01 [medline] PHST- 1995/05/01 00:00 [entrez] AID - 10.1152/ajplung.1995.268.5.L851 [doi] PST - ppublish SO - Am J Physiol. 1995 May;268(5 Pt 1):L851-5. doi: 10.1152/ajplung.1995.268.5.L851.