title: The flavonone naringenin inhibits chloride secretion in isolated colonic epithelia.
abstract: Studies investigating the activating and inhibitory actions of bioflavonoids on colonic function have yielded conflicting results. At low concentrations, flavonoids may stimulate chloride secretion while at higher concentrations they may have antisecretory actions in the colon. Naringenin (4',5,7-trihydroxyflavanone), found predominantly in citrus fruits, confers a protective effect against colorectal cancer and is purported to modulate secretory function in colonic cell lines. The aim of this study was to investigate the effects of naringenin on ion transport in rat and human colonic mucosae. Naringenin inhibited basal and stimulated chloride secretion in rat and human colonic mucosae mounted in Ussing chambers (IC(50) 330 μMol/L and 360 μMol/L respectively) and did not alter intracellular cAMP generation. Naringenin inhibited chloride secretion in MQAE (N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide) loaded crypts stimulated with forskolin. In BCECF (2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein acetoxymethyl ester) loaded crypts, naringenin caused an intracellular acidification (ΔpH/min=0.05 ± 0.004) which was sensitive to the Na-K-Cl co-transporter (NKCC) inhibitor bumetanide. In addition, the antisecretory effect of naringenin was not inhibited by blockade of barium sensitive basolateral K(+) transporters or by inhibition of Na+/H(+) exchange by amiloride. We propose that the antisecretory action of naringenin is due to inhibition of basolateral NKCC1 in rat and human colon.
authors.affiliation: College of Life Sciences & Conway Institute, National University of Ireland, Dublin, Ireland.
authors.forename: Danielle
authors.initials: D
authors.lastname: Collins
authors.forename: Sascha
authors.initials: S
authors.lastname: Kopic
authors.forename: John P
authors.initials: JP
authors.lastname: Geibel
authors.forename: Aisling M
authors.initials: AM
authors.lastname: Hogan
authors.forename: Mekki
authors.initials: M
authors.lastname: Medani
authors.forename: Alan W
authors.initials: AW
authors.lastname: Baird
authors.forename: Desmond C
authors.initials: DC
authors.lastname: Winter
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002712:Chlorides; D044950:Flavanones; D000242:Cyclic AMP; C005273:naringenin