The Effect of Hyperosmosis on Paracellular Permeability in Caco-2 Cell Monolayers

Abstract

The intestinal epithelium is a significant barrier to oral absorption of hydrophilic compounds, and their passage through the intercellular space is restricted by the tight junctions. In this study we found that hyperosmosis is a significant factor altering paracellular transport in Caco-2 cell monolayers. Osmotic regulators, such as sodium chloride, mannitol, and raffinose, decreased transepithelial electrical resistance and enhanced lucifer yellow permeability. The effect of these osmotic regulators on Caco-2 cell monolayers was not likely to be caused by gross cytotoxicity. Although certain amino acids and oligosaccharides have been reported to have specific tight junction-modulating activity, we found that the increased paracellular permeability of Caco-2 monolayers induced by these compounds was at least partly due to the increased osmotic pressure of the test solutions. These findings provide a new potential precaution in the evaluation of paracellular permeability-modulating substances using the Caco-2 cell monolayer system.

Cellular Entry of G3.5 Poly (amido amine) Dendrimers by Clathrin- and Dynamin-Dependent Endocytosis Promotes Tight Junctional Opening in Intestinal Epithelia

“…LY apparent permeability was less than 1×10 −6 for all conditions tested, which is within the accepted range of LY permeability for differentiated monolayers (23). There was not a significant difference between LY permeability in the presence of HBSS or inhibitors, confirming that endocytosis inhibitors do not affect tight junctional integrity (data not shown).…”

In vitro transport characteristics of EFdA, a novel nucleoside reverse transcriptase inhibitor using Caco-2 and MDCKII cell monolayers

“…LY (Mw: 457.2 Da), a known hydrophilic fluorescent paracellular marker (Inokuchi et al, 2009; Coyuco et al, 2011), was used as the positive control. As shown in Figs.…”

Increased osmolality enhances the tight junction‐mediated barrier function in a cultured renal epithelial cell line

“…Experimental evidence has pointed out that changes in osmolarity (hypo or hyperosmolality) can affect epithelial transport (Ikari et al, 2013(Ikari et al, , 2015Tokuda et al, 2016). However, these studies are highly controversial: while some results indicate a significant disruption of the paracellular barrier (H€ ogman et al, 2002;Brown et al, 2004;Inokuchi et al, 2009), others show an enhancement of this barrier mediated by TJ after increasing the osmolarity (Ikari et al, 2012(Ikari et al, , 2013(Ikari et al, , 2015. In addition, most of these studies focus on the effect of osmotic stress (using highly hyperosmotic solutions; >500 mOsm/kg H 2 O) rather than looking at the effect of a more physiologically relevant osmotic level.…”