TJ proteins are dysregulated or can be genetically defective in numerous diseases, which may lead to three effects: i) impaired
paracellular transport causing magnesium loss in the kidney, ii) increased
paracellular transport of solutes and water causing leak-flux diarrhea, and iii) increased permeability to large molecules (23).
To evaluate functionality of the diffusional barrier in more detail, the transport of sodium fluorescein (NaFlu), a hydrophilic molecule typically used to evaluate
paracellular transport, was monitored.
TJ is generated by the assembly of multiple proteins located near the apical part of the epithelium between neighboring cells (Figure 2) and controls the permeability of the
paracellular transport pathway.
Food and nutrients are absorbed into enterocytes and later the capillaries via transcellular and
paracellular transport. Sugar absorption studies show an increased absorption of transfer proteins in the small and large bowel, suggesting disruption of the intestinal membrane [2].
TJ or zonula occludens (ZO) are the first and the least permeable membrane for
paracellular transport of proteins formed by several transmembrane proteins, and they connect intercellularly to one another between cells in the extracellular space.
Previously, it was reported that gliadin crosses the epithelium through
paracellular transport. The
paracellular transport relies on intestinal permeability.
However, it is still controversial as to which degree other routes of water transport play a role, e.g., diffusional
paracellular transport directly through cell-cell junctions (Hill and Shachar-Hill, 2006; Murakami et al., 2006; Fishbarg, 2010) and secondary active water transport through cotransporters for ions and metabolites (see Zeuthen, 2002).
11: Effect of extracellular calcium concentration on the
paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells.
[27] reported that the
paracellular transport of metformin was saturable, and perhaps coadministration of metformin and fiber saturated
paracellular transport.
TJs seal the intercellular spaces between cells and regulate
paracellular transport of water, ions, and solutes (Proksch et al.
As claudin-1 has two extra cellular loops that display variability in the distribution and number of charged residues, it is the major determinant of ionic selectivity in
paracellular transport processes (Gonzalez et al., 2008).
Therefore the enhancement of
paracellular transport path is most likely to be responsible for increased passive transport of calcium in the intestine of rats fed high calcium diet.