title: Carrier-mediated uptake of nobiletin, a citrus polymethoxyflavonoid, in human intestinal Caco-2 cells.
abstract: The mechanism of intestinal absorption of nobiletin (NBL) was investigated using Caco-2 cells. The uptake of NBL from the apical membranes of Caco-2 cells was rapid and temperature-dependent and the presence of metabolic inhibitors, NaN3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone, did not cause a decrease in NBL uptake. The relationship between the initial uptake of NBL and its concentration was saturable, suggesting the involvement of a carrier-mediated process. The Km and uptake clearance (Vmax/Km) values for NBL were 50.6 and 168.1μl/mg protein/min, respectively. This clearance value was about 9-fold greater than that of the non-saturable uptake clearance (Kd: 18.5μl/mg protein/min). The presence of structurally similar compounds, such as quercetin and luteolin, competitively inhibited NBL uptake. These results suggest that uptake of NBL from the apical membranes of Caco-2 cells is mainly mediated by an energy-independent facilitated diffusion process.
authors: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors: Osamu
authors: O
authors: Kimura
authors: Faculty of Nutritional Sciences, Nakamura Gakuen University, Jonan-Ku, Fukuoka 814-0198, Japan.
authors: Chiho
authors: C
authors: Ohta
authors: Faculty of Nutritional Sciences, Nakamura Gakuen University, Jonan-Ku, Fukuoka 814-0198, Japan.
authors: Nobuyuki
authors: N
authors: Koga
authors: Daiichi College of Pharmaceutical Sciences, Minami-Ku, Fukuoka 815-8511, Japan.
authors: Koichi
authors: K
authors: Haraguchi
authors: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
authors: Yoshihisa
authors: Y
authors: Kato
authors: School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. Electronic address: endotty@hoku-iryo-u.ac.jp.
authors: Tetsuya
authors: T
authors: Endo
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D002957:Citrus / Q000378:metabolism*; D047309:Flavones / Q000737:chemistry / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000737:chemistry; D007700:Kinetics; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047309:Flavones; D005419:Flavonoids; D010936:Plant Extracts; C008661:nobiletin
keywords: Caco-2 cells; Facilitated diffusion; Flavonoid; Nobiletin