Cellular localization and hormonal regulation of pancreatic intrinsic factor secretion in dogs

Gastric mucosal cells are considered to be the principal site of intrinsic factor (IF) production in most mammals. Recent observations in dogs suggest that the pancreas is the major site of IF production in this species. The present study was undertaken to determine the cellular origins of canine pancreatic IF by combining in situ hybridization with immunocytochemistry and to examine the potential role of physiological pancreatic secretagogues, cholecystokinin octapeptide (CCK-8) and secretin, as mediators of canine pancreatic IF secretion. A human IF cDNA 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 fundus, gastric gland cells in the pyloric antrum, and in secretory duct cells of the pancreas. Immunocytochemistry using antibody against rat IF confirmed that these cells, as well as secretory ducts of salivary glands, synthesized an immunoreactive protein. In stimulated secretions 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 stimulation were observed for IF or haptocorrin, although a synergistic effect was observed for trypsinogen. These findings demonstrate that IF is synthesized in the canine stomach, pancreas, and probably salivary glands and that CCK-8 mediates IF secretion from pancreatic duct cells.