Intracellular mediators in the process of secretory diarrhea

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Changes of intracellular mediators were determined in the process of secretory and hemorrhagic diarrhea induced by various kinds of bacterial toxins. The following results were obtained;1) Cholera toxin (CT), heat labile toxin (LT) from E. coli, clostridium difficile toxin were administered into the jejunal loop of rats. CT and LT both activated A-kinase in the intestinal epithelial cells, while clostridium toxin induced secretory diarrhea via mechanism of Ca^<++>-mediated processes. But there is possibility that cytosolic free Ca^<++> of epithelial cells may play a role after A-kinase was activated in the process of CT-induced secretory diarrhea.2) Increased activity of brush-border enzyme alkaline phosphatase (ALP) was recognized in CT-induced secretory diarrhea. In order to see the relation between membrane component which was specifically phosphorylated by CT and bush border ALP, phosphorylated fraction was compared with this BBM enzyme. The phosphorylated fraction was recognized t … More o be a 105KDa protein, which was different from ALP as determined by specific antibody against ALP.3) The alteration of Ca^<++> concentration was determined in intestinal epithelial cells, endothelial cells and leukocytes under fluorescence microscopy. Clostridium toxin and verotoxin (VT) was shown to increase free Ca^<++> concentration in leukocytes, while CT did not influence the Ca^<++> concentration of leukocytes.(4) Diameter, flow velocity and vascular permeability of intestinal microvessels were observed under intravital microscopy. After CT administration, enlargement of venules and increased blood flow were observed accompanying with the increased vascular permeability. Clostridium toxin and VT induced the decrease in blood flow and also induced leukocyte sticking in venules and hemorrhagic lesions in the intestinal mucosa. These lesions were inhibited by PAF- and Ca^<++>- antagonist suggesting that various vasoactive substances and leukocytes play major roles in the development of hemorrhagic diarrhea. Less