Polarized transport of hydrophilic compounds across rat colonic mucosa from serosa to mucosa is temperature dependent.

Abstract

In both clinical and experimental studies, intestinal epithelial barrier function is routinely assessed by measuring mucosal permeability to various hydrophilic compounds. We performed experiments to determine whether permeation of several hydrophilic compounds across rat colonic mucosa is polarized. Sheets of colonic mucosa, stripped of the underlying seromuscular coats, were mounted in Ussing chambers. The rates of permeation across colonic mucosa by numerous hydrophilic compounds (fluorescein isothiocyanate [FITC]-dextrans with molecular weights of 4000 [FD4] and 70,000 [FD70] daltons, fluorescein disulfonic acid [FS], lucifer yellow [LY], lactulose, and mannitol) were several times greater in the serosal-to-mucosal (S-->M) direction than in the opposite direction. Increased S-->M permeation by FD4, lactulose, and mannitol was evident at 37 degrees C, but not at 4 degrees C. Efflux of FD4 and FS in the S-->M direction was dose-dependently inhibited by verapamil, an inhibitor of the P-glycoprotein efflux system. Indomethacin, an anion transporter inhibitor, showed no effect on the S-->M permeation of FD4, FD70, FS, or LY. Adding an excess of unlabeled dextran (mol wt, 10,000 daltons) dose-dependently decreased the S-->M efflux of FD4, but not FS or LY. The transport across rat colonic mucosa of a number of hydrophilic substances, including some compounds that are commonly used to measure intestinal permeability in clinical practice, is greater in the S-->M than in the M-->S direction. S-->M transport of these hydrophilic solutes is temperature dependent, suggesting that the process is an active one. S-->M transport of FD4 may occur via a process that manifests some degree of substrate specificity for polysaccharides.