Permeability characteristics of polyamines across intestinal epithelium using the Caco-2 monolayer system: comparison between transepithelial flux and mitogen-stimulated uptake into epithelial cells

Abstract

The polyamines putrescine, spermidine, and spermine are present in foods in high amounts, and are used for cell growth throughout the body. Surprisingly little is known about the mechanisms of polyamine absorption in the gut. To elucidate the mechanisms, transepithelial transport of polyamines was studied in human enterocytelike Caco-2 cells, grown on permeable filter supports. Transport of all three polyamines across Caco-2 cell monolayers was linear; intraepithelial accumulation of polyamines was higher in confluent than in differentiated Caco-2 cells, but still negligible in comparison with the overall transport across the monolayers. Epidermal growth factor (EGF) enhanced polyamine accumulation in Caco-2 cells four-fold, and basolateral uptake was higher than apical uptake if the cells were stimulated to grow. The amounts of polyamines taken up by the cells were nevertheless negligible in comparison with the net polyamine flux across the monolayers. Basolateral excretion of polyamines was in the picomolar range, whereas their transepithelial transport, occurring presumably by passive diffusion through the paracellular pathway, contributed hundreds of micromoles of polyamines to the basolateral chamber. We conclude that transepithelial transport of polyamines occurs by passive diffusion, and that it is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.