From the Guidelines
Secretin stimulates pancreatic bicarbonate secretion.
Mechanism of Stimulation
- The presence of nutrients in the duodenal lumen, particularly fats and acids, stimulates the release of secretin and cholecystokinin (CCK), which in turn stimulate pancreatic bicarbonate secretion 1.
- Vagal-cholinergic reflexes and the release of regulatory peptides, such as CCK, also play a role in mediating postprandial stimulation of human pancreatic secretion 1.
- The anatomic site of nutrient administration determines the degree and extent of pancreatic stimulation, with duodenal perfusion being a powerful stimulus for exocrine pancreatic secretion 1.
Importance of Pancreatic Bicarbonate Secretion
- Pancreatic bicarbonate secretion is essential for neutralizing gastric acid and maintaining an optimal pH for enzyme activity in the duodenum 1.
- The timed and coordinated release of pancreatic enzymes and bicarbonate into the duodenal lumen is necessary for undisturbed digestion and nutrient absorption 1.
From the Research
Pancreatic Bicarbonate Secretion Stimulants
- Secretin is a primary stimulant for pancreatic bicarbonate secretion, as shown in studies 2, 3, 4
- Cholecystokinin-octapeptide (CCK) can potentiate the effect of secretin on pancreatic bicarbonate secretion, but only at relatively small doses 2
- Vasoactive intestinal peptide (VIP) may also play a role in stimulating pancreatic ductal bicarbonate secretion, particularly in the presence of VIP-1 receptors 5
Mechanisms of Action
- Secretin acts on its family B G protein-coupled receptor to stimulate pancreatic and biliary ductular bicarbonate and water secretion 3
- CCK can act as a neurotransmitter by stimulating cholinergic neurons, which in turn can stimulate pancreatic secretion 6
- The increase in pancreatic bicarbonate secretion is associated with a fall in pancreatic interstitial pH, which is accompanied by an increase in pancreatic blood flow 4
Receptor Binding and Biological Activity
- The residues most critical for secretin receptor binding and biological activity are distributed throughout the entire length of the peptide 3
- Leu19 is uniquely important for secretin, and its mutation to alanine can destabilize the peptide and reduce its biological activity 3
- VIP-1 receptors are expressed on the majority of neoplastic pancreatic duct epithelial cells, and VIP can stimulate growth of VIP-1 receptor-bearing cells in vitro 5