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Uptake, Transport and Metabolism of Exogenous Nucleosides in Intestinal Epithelial Cell Cultures1,2,

Youping He, Ian R. Sanderson and W. Allan Walker3

Developmental Gastroenterology Laboratory, the Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129

The uptake and transport of nucleosides (adenosine, cytidine, guanosine, thymidine, uridine and inosine) were examined in intestinal cell lines (Caco-2 and IEC-6). Well-differentiated Caco-2 cells took up significantly more uridine and thymidine than less-differentiated cells over 24 h. These differences were reflected in the resulting trichloroacetic acid-soluble (nucleotide, nucleoside and nucleobase) pool sizes rather than in differences in nucleic acid incorporation. IEC-6 cells have smaller soluble pools than Caco-2 cells, and the uptake of nucleosides over 60 min reflected this difference. Caco-2 cells transported significantly more thymidine, cytidine, guanosine, adenosine and inosine into acid-soluble pools than IEC-6 cells. Caco-2 cells were grown on filters to examine the transcellular transport of nucleosides and to examine the chemical form in which nucleosides appeared at the basolateral aspect of the cell monolayer. The pattern of transport varied for individual nucleosides. The transport of cytidine and guanosine was significantly greater in the apical-to-basolateral direction than in the opposite direction over 2 h. No purine nucleoside was transported intact across the Caco-2 cell monolayer in either direction, with the majority of the transported material appearing as nucleobases. Nucleobases also represented the main metabolites of pyrimidines transported. However, some cytidine and uridine were detectable, but each constituted <20% of transported material. Nucleosides are therefore transported by enterocytes but metabolized during transport.


KEY WORDS: • Caco-2 cells • IEC-6 cells • nucleosides • uptake • transport

1 Supported by grants from the National Institute of Health (HD-12437, HD-31852 and DK-33506) and by grants from Wyeth-Ayerst Research Division of Clinical Nutrition and Critical Care of America.

2 The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

3 To whom correspondence should be addressed.

Manuscript received 20 April 1993. Revision accepted 18 March 1994.




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E. Errasti-Murugarren, M. Pastor-Anglada, and F. J. Casado
Role of CNT3 in the transepithelial flux of nucleosides and nucleoside-derived drugs
J. Physiol., August 1, 2007; 582(3): 1249 - 1260.
[Abstract] [Full Text] [PDF]




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