Pancreatic duct and microvascular permeability to macromolecules. The relation to acute pancreatitis.
In a model of acute pancreatitis which requires that pancreatic enzymes leak from a permeable duct, we studied the role of intravenous enterokinase (195,000 daltons) in pancreatic enzyme activation. Anesthetized cats were given intravenous 16,16-dimethyl prostaglandin E2 to increase pancreatic blood flow and microvascular permeability. In some animals the permeability of the pancreatic duct was increased by perfusion of the duct with glycodeoxycholic acid (7.5 mM). Endogenous enzyme secretion was stimulated by IV CCK and secretin. Some cats also received enterokinase intravenously. Those animals that received PGE2, glycodeoxycholate, and enterokinase all developed pancreatitis. When any of these agents were not given the pancreases appeared normal. These findings were consistent with the hypothesis that intravenous enterokinase leaked from small pancreatic blood vessels into the pancreatic parenchyma and/or ducts where activation of pancreatic enzymes occurred. The development of pancreatitis appeared to require an increase in both microvascular and ductal permeability.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D004195:Disease Models, Animal; D004765:Enteropeptidase / Q000494:pharmacology; D006002:Glycodeoxycholic Acid / Q000494:pharmacology; D010179:Pancreas / Q000098:blood supply*; D010183:Pancreatic Ducts / Q000503:physiopathology*; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D010316:Particle Size; D010539:Permeability
D006002:Glycodeoxycholic Acid; D004765:Enteropeptidase; D015064:16,16-Dimethylprostaglandin E2