Intestinal absorption of RU 41740, an immunomodulating compound extracted from Klebsiella pneumoniae, across duodenal epithelium and Peyer's patches of the rabbit

Abstract

The intestinal transport and degradation of RU 41740, an immunomodulating compound, were tested in vitro across rabbit duodenal epithelium and Peyer's patches mounted in Ussing chambers. Quantification of transport and metabolic behaviour across the intestinal wall were examined using tritiated RU 41740 ([ 3H]RU 41740). The viability of the tissues was assessed by recording electrical parameters. Transepithelial [ 3H]RU 41740-equivalent fluxes from mucosa to serosa were determined and the intracellular catabolism was examined by gel filtration of serosal [ 3H]products on a Sephacryl S-300 column after 2 h of experimentation. Steady-state transport rates were obtained after 60 min; transepithelial fluxes of [ 3H]RU 41740 equivalents were greater across the duodenum than the Peyer's patches (1647 ± 277 ng · h −1 · cm −2 versus 357 ± 61 ng · h −1 · cm −2). Elution profiles of the tritiated-degraded products in the serosal compartment indicated that the radioactivity was mainly associated with low molecular weight fragments (mol. wt. < 10,000) in the duodenum, whereas higher molecular weight fragments were found in the Peyer's patches. These results indicate that RU 41740, like most macromolecules, is transported across the intestinal epithelium by endocytosis with subsequent extensive degradation probably at the lysosomal level. However, the minor fraction transported intact as well as under high molecular weight products in the Peyer's patches might have an important effect on the underlying immune system.