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Nutrient Metabolism

Guanidine Transport across the Apical and Basolateral Membranes of Human Intestinal Caco-2 Cells Is Mediated by Two Different Mechanisms¹

Emanuela Cova², Umberto Laforenza, Giulia Gastaldi, Yula Sambuy^*, Simona Tritto, Alide Faelli and Ulderico Ventura

Institute of Human Physiology, University of Pavia, Pavia, Italy; ^* National Research Institute for Food and Nutrition, Rome, Italy; Department of General Physiology and Biochemistry, University of Milan, Milan, Italy

²To whom correspondence and reprint requests should be addressed. E-mail: emanuela{at}unipv.it.

The functional characteristics of the intestinal absorption and secretion of guanidine as a model of a nutritionally and metabolically essential organic cation were examined in the Caco-2 human intestinal cell line. Both apical and basolateral transport of [¹⁴C]-guanidine were studied using Caco-2 cells grown on polycarbonate permeable membranes. The basolateral-to-apical flux of [¹⁴C]-guanidine (i.e., its secretion) was quantitatively higher than the apical-to-basolateral transport (i.e., its absorption). When Na⁺ was replaced by K⁺ or Li⁺, both apical and basolateral accumulation were significantly inhibited. Studies using the cell monolayers and apical membrane vesicles obtained from Caco-2 cells showed a potential-independent mechanism of guanidine apical uptake and efflux. Conversely, basolateral uptake and efflux were membrane potential dependent. Kinetic analysis revealed that both saturable and nonsaturable mechanisms accounted for the apical and basolateral accumulations. The [¹⁴C]-guanidine efflux from cells through the apical and basolateral membranes was significantly reduced at 4°C, suggesting carrier-mediated mechanisms. Moreover, the apical efflux was stimulated by an inwardly directed H⁺ gradient. Influx and efflux of [¹⁴C]-guanidine were unaffected by the presence of tetraethylammonium, cimetidine or decynium-22 in the donor compartment. Only quinine significantly reduced [¹⁴C]-guanidine entrance through apical and basolateral membranes and its exit through the basolateral membrane. In conclusion, our results suggest that the influx and the efflux through the apical membrane is mediated by different transporters, whereas transport across the basolateral membrane is mediated by a member of the organic cation transporter family with high affinity for guanidine.

KEY WORDS: • guanidine • transepithelial transport • Caco-2 cells • apical and basolateral membranes • efflux