CELLULAR-LOCALIZATION AND HORMONAL-REGULATION OF PANCREATIC INTRINSIC-FACTOR SECRETION IN DOGS

Gastric mucosal cells are considered to be the principal site of intri nsic factor (IF) production in most mammals. Recent observations in do gs suggest that the pancreas is the major site of IF production in thi s species. The present study was undertaken to determine the cellular origins of canine pancreatic IF by combining in situ hybridization wit h immunocytochemistry and to examine the potential role of physiologic al pancreatic secretagogues, cholecystokinin octapeptide (CCK-8) and s ecretin, as mediators of canine pancreatic IF secretion. A human IF cD NA probe (J. Hewitt et al., Genomics 10: 432-440, 1991), validated for use in the dog, identified IF mRNA in parietal cells in the gastric f undus, gastric gland cells in the pyloric antrum, and in secretory duc t cells of the pancreas. Immunocytochemistry using antibody against ra t IF confirmed that these cells, as well as secretory ducts of salivar y glands, synthesized an immunoreactive protein. In stimulated secreti ons of anesthetized dogs, mean 45-min outputs of IF, haptocorrin, and trypsinogen were 13-, 8-, and 16-fold greater during stimulation with CCK-8 than with secretin. No synergistic effects of combined stimulati on were observed for IF or haptocorrin, although a synergistic effect was observed for trypsinogen. These findings demonstrate that IF is sy nthesized in the canine stomach, pancreas, and probably salivary gland s and that CCK-8 mediates IF secretion from pancreatic duct cells.