title: Flavone potently stimulates an apical transporter for flavonoids in human intestinal Caco-2 cells.
abstract: METHODS
  Based on the studies suggesting that active transport mechanisms contribute to the absorption of flavonoids into human intestinal Caco-2 cells, we here used the structurally similar fluorescent rhodamine 123 to test a possible influence of flavonoids on its uptake.
  
  
  RESULTS
  Rhodamine absorption displayed saturation kinetics with a K(m)  of 1.1 μM and a pH-optimum of 8.5 and was stimulated by flavone four-fold in its V(max) . Ring C of the other 16 flavonoids tested turned out to be of special importance in order to act as potent inhibitors for rhodamine transport, with a positive charge there, as present in the anthocyanidins, or a 2,3 double bond together with an aromatic ring fused to position 2, as present in flavones and flavonols, being essential structural requirements. Flavone-stimulated rhodamine uptake was unaffected by classical substrates of organic cation transporters or inhibitors of adenosine triphosphate (ATP)-dependent efflux pumps. Also, inhibitors of mitogen-activated protein kinases or tyrosine kinases did not influence the transport, whose stimulation, however, was essentially dependent on the simultaneous presence of flavone. The existence of a flavone-activated apical flavonoid transporter in Caco-2 cells was finally associated with the potently diminished transepithelial apical to basolateral fluxes of (14) C-kaempferol in the presence of competing unlabeled flavonoid substrates.
  
  
  CONCLUSIONS
  In conclusion, flavone activates an as yet unidentified transporter for flavonoids in the apical membrane of Caco-2 cells.
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Giessen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lies
authors.forename: Stefan
authors.initials: S
authors.lastname: Martens
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Boll
authors.forename: Uwe
authors.initials: U
authors.lastname: Wenzel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000042:Absorption; D000872:Anthocyanins / Q000494:pharmacology; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D044949:Kaempferols / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012235:Rhodamines / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000872:Anthocyanins; D002352:Carrier Proteins; D002712:Chlorides; D047309:Flavones; D005419:Flavonoids; D044949:Kaempferols; D027701:Organic Cation Transport Proteins; D012235:Rhodamines; D012964:Sodium; D014700:Verapamil; D011505:Protein-Tyrosine Kinases; D019791:Guanidine; C043562:flavone