| Pharmaceutical Application: |
Secretin human |
| Applications: |
Indicated for the stimulation of pancreatic secretions, including bicarbonate, to aid in the diagnosis of pancreatic exocrine dysfunction.gastrin secretion to aid in the diagnosis of gastrinoma. The product to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP). |
| Examples of Clinical Use: |
Pancreatic exocrine dysfunction and gastrinoma |
| Pharmacodynamics: |
In clinical trials, intravenous administration of synthetic human secretin stimulated the exocrine pancreas to promote juice and bicarbonate secretion, with variable responses depending on the pancreatic function of the individual. Having an identical amino acid sequence to the biologically-derived secretin, synthetic human secretin exhibits an equivalent biological activity as the natural hormone. The biological activity of synthetic human secretin was approximately 5.0 CU per mcg. In patients with suspected or known exocrine pancreatic dysfunction, a volume response of less than 2 mL/kg/hr, peak bicarbonate concentration of less than 80 mEq/L, and a bicarbonate output of less than 0.2 mEq/kg/hr following intravenous synthetic human secretin. Administration in healthy subjects in three crossover studies led to overall pancreatic secretory response of a mean peak bicarbonate concentration of 100 mEq/L, a mean total volume over one hour of 260.7 mL, and a peak bicarbonate concentrations ≥ 80 mEq/L. In a baseline-controlled study of patients with acute and acute recurrent pancreatitis undergoing magnetic resonance cholangiopancreatography (MRCP), administration of synthetic human secretin resulted in higher levels of sensitivity with minimal loss in specificity. This indicates that the stimulation of pancreatic secretions by synthetic secretin facilitates the diagnosis and clinical decision making of patients acute, acute recurrent, or chronic pancreatitis. |
| Mechanism of action: |
Synthetic human secretin mediates the same biological effects as the naturally-occurring gastrointestinal peptide hormone. Secretin is normally released from enterochromaffin cells and S cells in the intestinal mucosa of duodenum upon exposure of proximal intestinal lumen to the acidic gastric content, or fatty acids and amino acids. Secretin mediates an inhibitory effect on acid secretion by parietal cells of the stomach, and causes alkalinazation of the duodenal content by stimulating the release of pancreatic juice, which has high amounts of water and bicarbonate ions. Bicarbonate ions are released into the duodenum from the centroacinar cells, and epithelia lining the pancreatic and biliary ducts. Human secretin is a ligand at G-protein coupled secretin receptors which are expressed in the basolateral domain of several tissue cell types, including pancreas, stomach, liver, colon and other tissues. Upon interaction, levels of cAMP increase and initiates the cAMP-mediated signalling cascade that results in phosphorylation of protein kinase A (PKA) and activation of cystic fibrosis transmembrane conductance regulator (CFTR). Activation of CFTR activates Cl-/HCO3- anion exchanger 2 and leads to secretion of bicarbonate-rich-pancreatic fluid. Via the same cAMP signalling pathway, secretin promotes the secretion of water and electrolytes in cholangiocytes. Secretin may work through vagal-vagal neural pathways since stimulation of the efferent vagus nerve stimulates bicarbonate secretion and atropine blocks secretin-stimulated pancreatic secretion. Additionally, secretin acts as a diuretic to increase urinary volume and bicarbonate excretion. |
| Affected organisms: |
Not Available |
| Targets: |
Target 1. Secretin receptor |
