CARBACHOL, BUT NOT FORSKOLIN, INCREASES MUCOSAL-TO-SEROSAL TRANSPORT OF INTACT PROTEIN IN RAT ILEUM IN-VITRO

The effects of the secretagogues forskolin and carbachol on protein up take in isolated ileum of rats were studied. The mucosal-to-serosal tr ansport of horseradish peroxidase (HRP, mol mass 40 kDa) was measured in Ussing chambers, and afterwards tissues were processed for electron microscopy. In the absence of secretagogues, the flux of enzymaticall y active HRP was 5 pmol . cm(-2) . h(-1) at a mucosal concentration of 10 mu M Electron micrographs showed vesicles filled with active HRP i n enterocytes but no HRP activity in intercellular spaces. Forskolin d ecreased HRP activity in the cells. Carbachol increased the amount of HRP-filled vesicles in enterocytes and induced HRP filling in some int ercellular spaces and tight junctions in the upper parts of the villi. The transepithelial flux of intact HRP increased more than 2.5-fold. This effect was suppressed by atropine. We conclude that cholinergic a ctivation can increase the uptake of intact protein via endocytosis an d the transepithelial passage by the induction of a diffusional parace llular pathway. We speculate that the increased transport of intact pr otein through the intestinal barrier may influence immunologic sensiti zation to food allergens.