Efflux of sphingoid bases by P-glycoprotein in human intestinal Caco-2 cells.
The aim of this study was to determine whether sphingoid bases that originated from various dietary sources, such as mammals, plants, and fungi, are substrates for P-glycoprotein in differentiated Caco-2 cells, which are used as a model of intestinal epithelial cells. In Caco-2 cells, the uptake of sphingosine, the most common sphingoid base found in mammals, was significantly higher at physiological temperatures than those of cis/trans-8-sphingenine, trans-4, cis/trans-8-sphingadienine, 9-methyl-trans-4, trans-8-sphingadienine, or sphinganine. Verapamil, a potent P-glycoprotein inhibitor, increased the cellular accumulation of sphingoid bases, except for sphingosine, in a dose-dependent manner. Incubation with 1 microM digoxin for 48 h caused up-regulation of multidrug-resistance (MDR)1 mRNA and decreased the accumulation of sphingoid bases in Caco-2 cells, except for sphingosine. Thus P-glycoprotein probably contributes to the selective absorption of sphingosine from dietary sphingolipids in the digestive tract.
Sugawara
Tatsuya
T
Division of Food Science, Incorporated Administrative Agency, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 102-8471, Japan. sugawara@kais.kyoto-u.ac,jp
Kinoshita
Mikio
M
Ohnishi
Masao
M
Tsuzuki
Tsuyoshi
T
Miyazawa
Teruo
T
Nagata
Junichi
J
Hirata
Takashi
T
Saito
Morio
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D018938:Caco-2 Cells; D004077:Digoxin / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013379:Substrate Specificity; D015854:Up-Regulation / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D004077:Digoxin; D013110:Sphingosine