CYTOSKELETAL DISARRANGEMENT IN RAT INTESTINAL EPITHELIUM AFTER IN VIVO EXPOSURE TO SECRETAGOGUES

Abstract

Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) induced hypersecretion in the small intestine, as did cytochalasin B and dibutyryl-cAMP (DB-cAMP). The cytoskeleton in the apical part of the intestinal epithelial cells was disorganized after challenge with any of the 4 secretagogues, but not after cholera B subunit toxoid challenge, as revealed by immunofluorescence microscopy using actin and the intermediate filament keratin as markers. EM analysis confirmed the re-engagement of the terminal web and the appearance of short microvilli lacking most of their normally observed central core of actin filaments. Pretreatment with chloroquine prevented cytoskeletal disorganization and hypersecretion by CT, but not by cytochalasin B. A similar effect was achieved with chloroquine on CT-induced fluid secretion, while chlorpromazine inhibited the fluid response to cytochalasin B and to CT. The observed cytoskeletal re-engagement might be one of the reactions behind enterotoxic diarrhea.