Secretin

Structure

In 1970, the aa sequence of secretin was determined by Mutt to be a polypeptide comprising 27 aa residues. Secretin belongs to the secretin/glucagon superfamily, which shares significant structural and conformational homology. The family includes the vasoactive intestinal peptide (VIP), the pituitary adenylate cyclase activating peptide (PACAP), the growth hormone-releasing hormone (GHRH), peptide histidine isoleucine (PHI) or peptide histidine methionine (PHM), glucagon, glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), and the gastric inhibitory peptide (GIP). Secretin is highly conserved among mammalian species, but the sequence identity in nonmammalian species up to birds is lower than in mammals. Secretin-like sequences have not been found in teleost and lungfish genomes. Porcine secretin, Mr 3055; human secretin, 3039; chicken secretin, 3073. Soluble in water, physiological saline solution, and aqueous organic solvents. Stable in dilute hydrochloric acid at -20°C, but unstable in aqueous solution.

Gene, mRNA, and precursor

Human secretin is derived from a 121-aa residue secretin precursor consisting of a signal peptide, a short N-terminal peptide, secretin, and a C-terminal peptide. The human secretin precursor gene, SCT, location 11p15.5, consists of four exons, and the secretin coding region is exon 2. The chicken SCT gene consists of seven exons. Exons 1 and 2 are noncoding, exon 4 encodes the secretin-like peptide, and exon 5 encodes the secretin peptide.

Synthesis and release

Secretin is synthesized and secreted by S cells in the small intestine, and neurons in the brain. Secretin release is mainly stimulated by gastric acid delivered into the duodenal lumen. In addition, secretin is released by digested products of fat and protein. In canine duodenal mucosal explants, somatostatin did not alter the basal secretion of secretin but inhibited secretin secretion stimulated by pH 4.5. GABA stimulated both basal and pH 4.5-induced secretin secretion. In the brain, the estrogen-related receptor α upregulates the SCT promoter and gene expression.

Receptors

The receptor of secretin (SCTR) is a seventransmembrane GPCR that belongs to a subclass of the family B . The human SCTR consists of 440 aa residues that contain a large N-terminal extracellular domain. Cys residues and disulfide bonds in the extracellular domain have been suggested to play a key role in agonist binding.  The pathway is mainly coupled to the Gs protein. Secretin activates adenylate cyclase and stimulates the production of cAMP.

Biological functions

Using northern blotting analysis, human SCTR mRNA was detected in the pancreas, intestine, colon, kidney, lung, and liver. Secretin stimulates the secretion of bicarbonate, water, and electrolytes from the ductal epithelium. In the stomach, secretin acts as an enterogastrone that inhibits gastric acid release and gastric emptying. In the kidney, secretin regulates urine output and activates adenylyl cyclase in rats. In the brain, SCTR is widely distributed in the hippocampus, central amygdala, thalamus, hypothalamus, posterior pituitary, cerebellum, and medulla oblongata. Secretin regulates social interaction, water and food intake, motor coordination, and spatial and motor learning behaviors. The zebrafish secretin receptor has been shown to be nonbioactive.

Clinical implications

The stimulatory effect of secretin on pancreatic secretion has been used in a range of clinical applications. Zollinger-Ellison syndrome is caused by a gastrin-secreting tumor (gastrinoma), and the secretin test has been used for the diagnosis of the syndrome. In the secretin test, the gastrin level is raised after intravenous secretin administration in Zollinger-Ellison syndrome patients, but not in healthy individuals. Secretin is elevated in Zollinger-Ellison patients and in patients with duodenal ulcers. Secretin levels are low in patients with pernicious anemia and achlorhydria. A clinical trial of secretin in autism has been carried out, but the clinical efficacy remains unreliable.

Description

Secretin was the first hormone identified. It is a secretagogue of pancreatic digestive juices from the porcine duodenum, used to aid in the diagnosis of gastrinoma. Secretin was discovered by Bayliss and Starling in 1902 as a secretagogue of pancreatic juices from the porcine duodenum. It was the first hormone identified.

Uses

Stimulates pancreatic and gastric secretions to aid in the diagnosis of pancreatic exocrine dysfunction and the diagnosis of gastrinoma.

brand name

SecretinKabi (KabiVitrum, Sweden).

General Description

Secretin is a 27-amino-acid polypeptide that is structurallysimilar to glucagon. The presence of acid in the small intestineis the most important physiological stimulus for the secretionof secretin. The primary action of secretin is on pancreatic acinarcells that regulate the secretion of water and bicarbonate.Secretin also promotes the secretion of pancreatic enzymes, toa lesser extent. Secretin inhibits the release of gastrin and,therefore, gastric acid. It also increases stomach-emptyingtime by reducing the contraction of the pyloric sphincter.

Clinical Use

Recombinant human secretin (SecreFlo, ChiRhoStim) is approved for use in stimulating gastrin secretion to aid in the diagnosis of gastrinoma.