HGNC Approved Gene Symbol: SCTR
Cytogenetic location: 2q14.2 Genomic coordinates (GRCh38): 2:119,439,843-119,524,483 (from NCBI)
Secretin (SCT; 182099) occupies a unique position in the history of gastrointestinal hormones because it was the first to be discovered, in duodenal mucosa by Bayliss and Starling (1902). This 27-amino acid peptide stimulates the secretion of bicarbonate, enzymes, and potassium ion by the pancreas.
Ishihara et al. (1991) isolated a cDNA encoding the rat secretin receptor. The nucleotide sequence showed that the secretin receptor consists of 449 amino acids with a calculated molecular mass of 48.7 kD. It contains 7 putative transmembrane segments and belongs to a family of the G protein-coupled receptors, which includes parathyroid hormone receptor (168468), glucagon-like receptor (138032), and calcitonin receptor (114131).
Chow (1995) showed that the secretin receptor cDNA isolated from a pancreatic adenocarcinoma cell-line cDNA library was 1,717 bp long and encoded a 440-amino acid polypeptide. By Northern blot analysis, a 1.8-kb mRNA was detected in human pancreas and intestine, while weak hybridization signals were detected in human colon, kidney, and lung.
Mark and Chow (1995) mapped the SCTR gene to chromosome 2q14.1 by fluorescence in situ hybridization.
Chu et al. (2007) showed that Sctr-null mice developed mild polydipsia and polyuria associated with reduced renal expression of AqpP (107777) and Aqp4 (600308), as well as altered glomerular and tubular morphology, suggesting possible disturbances in filtration and/or water reabsorption. In vitro and in vivo mouse studies demonstrated a role for secretin in stimulating Aqp2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules, and expression of this water channel under hyperosmotic conditions. These findings identified a vasopressin (AVP; 192340)-independent mechanism for secretin in modulation of renal water reabsorption.
In rat brain, Chu et al. (2009) detected expression of secretin and its receptor in the hypothalamus, where they were distributed in magnocellular neurons in the supraoptic nucleus (SON) and in parvocellular and magnocellular neurons in the paraventricular nucleus (PVN). Expression was also observed in the posterior lobe of the pituitary. Intraventricular administration of SCT resulted in expression of Fos (164810) in the PVN and SON, indicating increased activity in these brain regions. Increased Fos expression was associated with induction of vasopressin gene expression and its secretion into the peripheral circulation. Sct and Sctr expression and Sct release were significantly increased in the hypothalamus and pituitary of hypovolemic mice. Chu et al. (2009) concluded that secretin is present throughout the hypothalamo-neurohypophysial axis and stimulates vasopressin expression in the hypothalamus and release from the posterior pituitary, which ultimately acts on the kidney to regulate water homeostasis. Secretin also acts as a neurosecretory factor that itself is released from the posterior pituitary under plasma hyperosmolality conditions, where it can act directly on the kidney.
Bayliss, W., Starling, E. H. The mechanism of pancreatic secretion. J. Physiol. (London) 28: 325-353, 1902.
Chow, B. K.-C. Molecular cloning and functional characterization of a human secretin receptor. Biochem. Biophys. Res. Commun. 212: 204-211, 1995. [PubMed: 7612008] [Full Text: https://doi.org/10.1006/bbrc.1995.1957]
Chu, J. Y. S., Chung, S. C. K., Lam, A. K. M., Tam, S., Chung, S. K., Chow, B. K. C. Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption. Molec. Cell Biol. 27: 2499-2511, 2007. [PubMed: 17283064] [Full Text: https://doi.org/10.1128/MCB.01088-06]
Chu, J. Y. S., Lee, L. T. O., Lai, C. H., Vaudry, H., Chan, Y. S., Yung, W. H., Chow, B. K. C. Secretin as a neurohypophysial factor regulating body water homeostasis. Proc. Nat. Acad. Sci. 106: 15961-15966, 2009. [PubMed: 19805236] [Full Text: https://doi.org/10.1073/pnas.0903695106]
Ishihara, T., Nakamura, S., Kaziro, Y., Takahashi, T., Takahashi, K., Nagata, S. Molecular cloning and expression of a cDNA encoding the secretin receptor. EMBO J. 10: 1635-1641, 1991. [PubMed: 1646711] [Full Text: https://doi.org/10.1002/j.1460-2075.1991.tb07686.x]
Mark, H. F. L., Chow, B. K.-C. Localization of the gene encoding the secretin receptor, SCTR, on human chromosome 2q14.1 by fluorescence in situ hybridization and chromosome morphometry. Genomics 29: 817-818, 1995. [PubMed: 8575789] [Full Text: https://doi.org/10.1006/geno.1995.9922]