@article{oai:niigata-u.repo.nii.ac.jp:00018506, author = {中澤, 俊郎}, issue = {7}, journal = {新潟医学会雑誌, 新潟医学会雑誌}, month = {Jul}, note = {The mechanism of diarrhea induced by Clostridium difficile (CD) toxin is not fully understood although that by Cholera toxin is sufficiently done. Present experiment aims to clarify its mechanism. Male Wistar rats weighing about 200 g were used, and CD toxin were injected into the lumen of ligated jejunal loops. First, time course study of histological examination and measurement of fluid accumulation in the ligated loops were carried out from 2 to 10 hours after CD toxin exposure. Second, we studied the changes of the activities of microvillus membrane enzymes and intestinal absorption rates of oligopeptides. Third, we studied the changes of activities of two intracellular mediators, protein kinase C (PKC) which is activated by diacylglycerol, and inositol 1-4-5-trisphosphate (IP_3) which releases Ca^<++> from endoplasmic reticulum. Diacyiglycerol and IP_3 are produced by receptor mediated-inositolphospholipid turnover. Luminal fluid accumulation steadily increased from 2 to 10 hours after CD toxin exposure. Slight damage in villus tips was observed 2 hours after exposure, and the change became more severe with time. Leucine aminopeptidase (LAP) activity was significantly decreased at 2 hours. The absorption rates of peptides were markedly decreased in toxin treated rats as compared with control rats using the jejunal perfusion method. Activity of PKC was significantly increased at 30 minutes, and that of IP_3 was also increased 1 hour after CD toxin exposure. In addition, PKC antagonist, staurosporin, inhibited the toxin induced-fluid accumulation. Calmodulin antagonists, trifluoperazine and chlorpromazine, also inhibited it. These results indicate that CD toxin increased inositolphospholipid turnover with subsequent activation of PKC and IP_3 in epithelial cell. Then inositolphospholipid turnover and Ca^<++> mobilization possibly play a synergistic role in inhibition of LAP and peptide carrier protein synthesis. Consequently inhibition of LAP synthesis and disturbance of peptide absorption may partly contribute to the CD toxin induced diarrhea.}, pages = {340--352}, title = {Clostridium difficile toxin 起因性下痢症における細胞内情報伝達機構と消化吸収障害の検討 : Cholera toxin 起因性下痢症と対比して}, volume = {109}, year = {1995} }