Molecular mechanisms of ion transport and clinical application

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1. Pancreatic HCOィイD23ィエD2ィイD1-ィエD1 and fluid secretion were studied by monitoring luminal pH and luminal volume simultaneously in interlobular duct segments (diameter〜100mm) is isolated from guinea-pig pancreas. We found that HCOィイD23ィエD2ィイD1-ィエD1 uptake across the basolateral membrane is achieved largely by NaィイD1+ィエD1-HCOィイD23ィエD2ィイD1-ィエD1 cotransport, and that HCOィイD23ィエD2ィイD1-ィエD1 efflux and fluid secretion across the luminal membrane involve HCOィイD23ィエD2ィイD1-ィエD1 conductance. The location of purinoceptors in pancreatic duct cells and their role in regulating HCOィイD23ィエD2ィイD1-ィエD1 and fluid secretion was studied in microperfused duct segments. We found that both apical and basolateral nucleotides inhibit it. The efficients of arginine vasopressin (AVP) on ductal secretion were studied in isolated vascularly perfused ductal fluid secretion via VィイD21ィエD2 receptors.2. We have adopted molecular methodologies to study water transport and cloned a new aquaporin from rat liver with high … More amino-acid sequence identify to human AQP9.3. We also conduct study of water and electrolytes transport in vivo. We found that guanylin and heat-stable enterotoxin administered into the lumen of rat jejunum caused fluid secretion. Intravenous guanylin induced mucus secretion from goblet cells in rat duodenal crypts.4. We have succeeded in a continuous and simultaneous measurement of pancreatic blood flow and pancreatic secretion in conscious dog. We found that pituitary adenylate cyclase activating peptide (PACAP) and vasoactive intestinal peptide (VIP) induced vasodilatation comparable to that observed after a meal.5. We have started to investigate the relationships between mutations in cystic fibrosis transmembrane conductance regulator (CFTR) and chronic pancreatitis in Japan.6. We examined the effects of phospholipase AィイD22ィエD2 (PLAィイD22ィエD2) inhibitors on CaィイD12+ィエD1 oscillations and amylase secretion in rat pancreatic acinar cells. We found that type IV (cytosolic)PLAィイD22ィエD2 regulates CaィイD12+ィエD1 signaling and enzyme secretion. Less