Nucleotide uptake and metabolism by intestinal epithelial cells

The epithelial cells of the gastrointestinal tract are the first to encounter ingested nucleotides. Enterocytes metabolize or transport nucleotides (often partially metabolized) to other cell types. Nucleotides may also affect enterocyte gene expression. These interactions in intestinal cell lines (Caco-2 and IEC-6 cells) are described. Nucleotides and nucleosides are efficiently taken up by neoplastic cells (Caco-2) and substantially metabolized during absorption by epithelial monolayers. In nonmalignant cells (IEC-6), nucleotide pools are smaller than enterocytes of neoplastic origin (Caco-2). Consequently, cell proliferation in IEC-6 cells is more dependent on an external supply of nucleotides. Cell differentiation was examined by measuring brush border enzyme activities (sucrase, lactase and alkaline phosphatase). Nucleotides enhanced the expression of brush border enzymes in carcinoma cells only when stressed by glutamine deprivation. IEC-6 cells, which are poorly differentiated in optimal media, require basement membrane (Matrigel) for expression of brush border enzymes. Under these conditions, adding nucleotides to the culture medium enhanced enzyme activity. In addition to being substrates for intestinal absorption, nucleotides may affect enterocyte differentiation.