Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea.

Abstract

TMEM16A was found recently to be a calcium-activated Cl(-) channel (CaCC). CaCCs perform important functions in cell physiology, including regulation of epithelial secretion, cardiac and neuronal excitability, and smooth muscle contraction. CaCC modulators are of potential utility for treatment of hypertension, diarrhea, and cystic fibrosis. Screening of drug and natural product collections identified tannic acid as an inhibitor of TMEM16A, with IC(50) ∼ 6 μM and ∼100% inhibition at higher concentrations. Tannic acid inhibited CaCCs in multiple cell types but did not affect CFTR Cl(-) channels. Structure-activity analysis indicated the requirement of gallic or digallic acid substituents on a macromolecular scaffold (gallotannins), as are present in green tea and red wine. Other polyphenolic components of teas and wines, including epicatechin, catechin, and malvidin-3-glucoside, poorly inhibited CaCCs. Remarkably, a 1000-fold dilution of red wine and 100-fold dilution of green tea inhibited CaCCs by >50%. Tannic acid, red wine, and green tea inhibited arterial smooth muscle contraction and intestinal Cl(-) secretion. Gallotannins are thus potent CaCC inhibitors whose biological activity provides a potential molecular basis for the cardioprotective and antisecretory benefits of red wine and green tea.

• Authors: Wan Namkung, Jay R Thiagarajah, Puay-Wah Phuan, A S Verkman
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 24 Issue 11 Pg. 4178-86 (Nov 2010) ISSN: 1530-6860 [Electronic] United States
• PMID: 20581223 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ANO1 protein, human
• Anoctamin-1
• Chloride Channels
• Hydrolyzable Tannins
• Membrane Proteins
• Neoplasm Proteins
• Tannins
• Tea

Topics

• Animals
• Anoctamin-1
• Cell Line
• Chloride Channels (antagonists & inhibitors)
• Humans
• Hydrolyzable Tannins (chemistry, pharmacology)
• Inhibitory Concentration 50
• Membrane Proteins (antagonists & inhibitors)
• Molecular Structure
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects)
• Neoplasm Proteins (antagonists & inhibitors)
• Rats
• Structure-Activity Relationship
• Tannins (pharmacology)
• Tea (chemistry)
• Wine