Luminal CCK and its neuronal action on exocrine pancreatic secretion.

Gut regulatory peptides are produced by mucosal endocrine cells and released both into the circulation as well as into the gut lumen. Following stimulation the distribution between the circulation and gut lumen changes in favor of the gut lumen. In the blood plasma, the biological half-life of gut regulatory peptides is counted in single minutes due to high aminopeptidase activity and liver extraction. In the gut lumen, however, regulatory peptides retain their biological activity much longer, especially in newborn and young animals. A series of studies was performed in neonatal calves and pigs to explore the role of luminal cholecystokinin (CCK) on the regulation of exocrine pancreatic secretion. In anaesthetized neonatal calves, CCK was secreted into the duodenal lumen, and electrical vagal stimulation increased CCK release into the duodenal lumen but not into the circulating blood. In conscious calves, luminal CCK-8 stimulated pancreatic protein secretion by a neurohormonal mechanism dependent on a duodenal mucosal CCK1 receptor and vagal nerve activity. Immunocytochemistry pointed to an association of mucosal CCK1 and CCK2 receptors with neuronal components in the small intestine of neonatal calves. Experiments in calves and pigs with CCK-8 infusions into the duodenal branches of the right gastroepiploic artery confirmed the results of luminal CCK-8 and questioned the physiological relevance of a direct mechanism of CCK on the pancreatic acini.