Brain-gut axis in the modulation of pancreatic enzyme secretion

Pancreatic enzyme secretion is controlled by complex of neurohormonal mechanisms, activated by nutrients. Food components in the duodenum acts as the signals for activation of intestinal phase of pancreatic secretion. Direct stimulation of pancreatic exocrine function involves several hormones, which bind to the receptors on pancreatic acinar cell. Indirect mechanism depends on the activation of autonomic nervous reflexes. Brain is also implicated in the regulation of pancreatic exocrine function. Dorsal vagal complex of the brainstem (DVC) appears the center of long vago-vagal cholinergic entero-pancreatic reflex. Mucosal terminals, which initiates entro-pancreatic reflex could be stimulated by CCK, serotonin and perhaps others peptides, which are released into duodenum from the enteroendocrine (EE) cells of the gastrointestinal mucosa. Melatonin, leptin and ghrelin are released from the EE cells into the gastrointestinal lumen. These substances given intraduodenally to the rats produced dose-dependent stimulation of pancreatic enzyme secretion, but they failed to affect directly amylase release from isolated pancreatic acini. Intraluminal application of melatonin, its precursor: L-tryptophan, leptin or ghrelin dose-dependently increased plasma CCK level. Above stimulatory effects of investigated substances on CCK release were completely abolished by bilateral, subdiaphragmatic vagotomy, capsaicin-deactivation of afferent nerves as well as blockade of CCK receptors. We conclude that melatonin, leptin or ghrelin, which are released into duodenal lumen by nutrients, stimulate pancreatic enzyme secretion by activation of CCK release and activation of duodeno-pancreatic reflex.