Efflux of sphingoid bases by P-glycoprotein in human intestinal Caco-2 cells

Tatsuya Sugawara, Mikio Kinoshita, Masao Ohnishi, Tsuyoshi Tsuzuki, Teruo Miyazawa, Junichi Nagata, Takashi Hirata, Morio Saito

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


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 sphingosime, 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 μM digoxin for 48 h caused up-regulation of murtidrug-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.

Original languageEnglish
Pages (from-to)2541-2546
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Issue number12
Publication statusPublished - 2004 Dec


  • Caco-2 cells
  • Murtidrug-resistance (MDR)1
  • P-glycoprotein
  • Sphingoid base
  • Sphingolipids

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry


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