title: Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.
abstract: ε-Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε-viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa-submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short-circuit current (Isc) and tissue conductance (Gt) were continuously measured. The mucosal addition of ε-viniferin (>10(-5) mol/L) and resveratrol (>10(-4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in Isc and a rapid phase decrease (P-1) followed by rapid (P-2) and broad (P-3) peak increases in Gt in concentration-dependent manners. Mucosal ε-viniferin (10(-4) mol/L), but not resveratrol (10(-4) mol/L), increased the permeability of FITC-conjugated dextran (4 kDa). The mucosal ε-viniferin-evoked changes in Isc (Cl(-) secretion), but not in Gt, were attenuated by a selective cyclooxygenase (COX)-1 inhibitor and a selective EP4 prostaglandin receptor. The mucosal ε-viniferin-evoked increase in Isc was partially attenuated, and P-2, but not P-1 or P-3, change in Gt was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε-viniferin concentration-dependently attenuated the mucosal propionate (1 mmol/L)-evoked increases in Isc and Gt Immunohistochemical studies revealed COX-1-immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε-viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX-1 and TRPA1. Moreover, mucosal ε-viniferin decreased mucosal sensitivity to other luminal molecules such as short-chain fatty acids. In conclusion, these results suggest that ε-viniferin modifies intestinal mucosal transport and barrier functions.
authors.affiliation: Laboratory of Physiology, Department of Environmental and Life Sciences, University of Shizuoka, Shizuoka, Japan karaki@u-shizuoka-ken.ac.jp.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Karaki
authors.affiliation: FANCL Research Institute, FANCL Corporation, Yokohama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ishikawa
authors.affiliation: Laboratory of Physiology, Department of Environmental and Life Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tomizawa
authors.affiliation: Laboratory of Physiology, Department of Environmental and Life Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Atsukazu
authors.initials: A
authors.lastname: Kuwahara
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007420:Intestine, Large / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001572:Benzofurans; D013267:Stilbenes; C091891:epsilon-viniferin; D000077185:Resveratrol
keywords: Epithelial ion transport; intestinal chemosensing; ussing chamber