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secretin receptor

Family: Glucagon receptor family

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
General Comments
References
Gene and Protein Information
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 440 2q14.1 SCTR secretin receptor 1,11,13
Mouse 7 337 1 E2.3 Sctr secretin receptor
Rat 7 449 13 Sctr secretin receptor 9
Previous and Unofficial Names
SCT-R
MGC93381
6530402O03Rik
Database Links
ChEMBL Target 147 (Hs)
DrugBank Target 352 (Hs)
Ensembl ENSG00000080293 (Hs), ENSMUSG00000026387 (Mm)
Entrez Gene 6344 (Hs), 319229 (Mm), 81779 (Rn)
GeneCards SCTR (Hs)
GenitoUrinary Development Molecular Anatomy Project Sctr (Mm)
HomoloGene 68290 (Hs)
Human Protein Reference Database 01628 (Hs)
InterPro P47872 (Hs), Q5FW12 (Mm), P23811 (Rn)
KEGG Gene hsa:6344 (Hs), mmu:319229 (Mm), rno:81779 (Rn)
OMIM 182098 (Hs)
PharmGKB Gene PA35018 (Hs)
PhosphoSitePlus P47872 (Hs), Q5FWI2 (Mm), P23811 (Rn)
Protein Ontology (PRO) PRO:000014544 (Hs)
RefSeq Nucleotide NM_002980 (Hs), NM_001012322 (Mm), NM_031115 (Rn)
RefSeq Protein NP_002971 (Hs), NP_001012322 (Mm), NP_112377 (Rn)
TreeFam ENSG00000080293 (Hs), ENSMUSG00000026387 (Mm)
UniGene Hs. 42091 (Hs)
UniProt P47872 (Hs), Q5FW12 (Mm), P23811 (Rn)
Wikipedia secretin receptor
Glucagon receptor family
Search for 3D structures on the PDB
Search by keyword: Glucagon receptor family secretin receptor Search by accession number: P23811, P47872, Q5FW12
Natural/Endogenous Ligand(s)
secretin {Sp: Rat} , secretin {Sp: Human} , secretin {Sp: Mouse}
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]secretin (pig) Rn Full agonist 7.7 – 9.2 pKd 9
[Bpa6,Tyr10]secretin-27 (rat) Rn Full agonist 7.6 pKd 4
secretin {Sp: Pig} Rn Full agonist 8.0 – 9.0 pKi 9
secretin {Sp: Rat} Rn Full agonist 8.0 – 9.0 pKi 4-5
secretin {Sp: Human} Hs Full agonist 9.7 pEC50 1
secretin {Sp: Pig} Rn Agonist 9.0 pIC50 6
[Arg16]chicken secretin Rn Agonist 7.7 pIC50 6
VIP {Sp: Human, Mouse, Rat} Rn Agonist 6.2 pIC50 6
VIP {Sp: Human, Mouse, Rat} Hs Partial agonist 5.4 pIC50 9
secretin-(5-27) (pig) Rn Full agonist 5.0 pIC50 9
View species-specific agonist tables
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[(CH2NH)4,5]secretin Hs Antagonist 5.3 pKi 7
Primary Transduction Mechanisms
Transducer Effector/Response
Adenylate cyclase stimulation
Calcium channel
References: 
Tissue Distribution
Duodenum, jejunum, pancreas, tertiary bronchus, lung parenchyma and pulmonary artery.
Species:  Human
Technique:  RT-PCR.
References:  3
Cerebellum, central amygdala, hippocampus, area postrema and the nucleus of the tractus solitary.
Species:  Rat
Technique:  RT-PCR.
References:  16
Jejunum, pancreas, epididymis.
Species:  Rat
Technique:  RT-PCR.
References:  2
Epididymis: Principle cells of the capus region > initial segement.
Species:  Rat
Technique:  Western blotting.
References:  2
Expression Datasets

Click here to show/hide data

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cAMP levels in CHO cells transfected with the secretin receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of cAMP accumulation.
References:  14
Measurement of the extracellular acidification rate in CHO cells transfected with the human secretin receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Increase in ectracellular acidification rate.
References:  14
Measurement of short-circuit current (Isc) caused by chloride and bicarbonate secretion in cultured epididymal epithelia.
Species:  Human
Tissue:  Cultured epididymal epithelia.
Response measured:  Stimulation of Isc.
References:  2
Physiological Functions
Secretin activates GABA release both directly and indirectly via glutamate release.
Species:  Rat
Tissue:  Cerebellum.
References:  12
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0003009 abnormal cytokine secretion PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0000521 abnormal kidney cortex PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0003014 abnormal kidney medulla morphology PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0009643 abnormal urine homeostasis PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0005618 decreased potassium excretion PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0005570 decreased sodium excretion PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0002988 decreased urine osmolality PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0004860 dilated kidney collecting duct PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0005559 increased circulating glucose level PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0005425 increased macrophage cell number PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0001859 kidney inflammation PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0001426 polydipsia PMID: 17283064 
Sctrtm1Bkcc Sctrtm1Bkcc/Sctrtm1Bkcc
B6.129S7-Sctr		 MGI:2441720  MP:0001762 polyuria PMID: 17283064 
General Comments
There appear to be important species differences in the cellular and organ distribution of secretin and secretin family receptors. The best example of this is the confusing series of observations in pancreas of guinea-pig, rat, and human[10,15]. There are also differences in the pharmacologic profile of secretin receptors from different species, despite minimal changes in primary structure. Rat and human secretin receptors have very different binding affinities for VIP that have been attributed to a single receptor residue[8].

REFERENCES

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1. Chow, B. K. (1995) Molecular cloning and functional characterization of a human secretin receptor. Biochem. Biophys. Res. Commun., 212: 204-211. [PMID:7612008]

2. Chow, B. K., Cheung, K. H., Tsang, E. M., Leung, M. C., Lee, S. M. and Wong, P. Y. (2004) Secretin controls anion secretion in the rat epididymis in an autocrine/paracrine fashion. Biol Reprod, 70: 1594-1599. [PMID:14749298]

3. Davis, R. J., Page, K. J., Dos Santos Cruz, G. J., Harmer, D. W., Munday, P. W., Williams, S. J., Picot, J., Evans, T. J., Sheldrick, R. L., Coleman, R. A. and Clark, K. L. (2004) Expression and functions of the duodenal peptide secretin and its receptor in human lung. Am J Respir Cell Mol Biol, 31: 302-308. [PMID:15191914]

4. Dong, M., Wang, Y., Hadac, E. M., Pinon, D. I., Holicky, E. and Miller, L. J. (1999) Identification of an interaction between residue 6 of the natural peptide ligand and a distinct residue within the amino-terminal tail of the secretin receptor. J Biol Chem, 274: 19161-19167. [PMID:10383421]

5. Ganguli, S. C., Park, C. G., Holtmann, M. H., Hadac, E. M., Kenakin, T. P. and Miller, L. J. (1998) Protean effects of a natural peptide agonist of the G protein-coupled secretin receptor demonstrated by receptor mutagenesis. J Pharmacol Exp Ther, 286: 593-598. [PMID:9694908]

6. Gourlet, P., Vandermeers, A., Vertongen, P., Rathe, J., De Neef, P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (1997) Development of high affinity selective VIP1 receptor agonists. Peptides, 18: 1539-1545. [PMID:9437714]

7. Haffar, BM; Hocart, SJ; Coy, DH; Mantey, S; Chiang, HC; Jensen, RT. (1991) Reduced peptide bond pseudopeptide analogues of secretin. A new class of secretin receptor antagonists. J. Biol. Chem., 266 (1): 316-22. [PMID:1702423]

8. Holtmann, M. H. and Miller, L. J. (1996) Molecular basis and species specificity of high affinity binding of vasoactive intestinal polypeptide by the rat secretin receptor. J. Pharmacol. Exp. Ther., 279: 555-560. [PMID:8930157]

9. Ishihara, T., Nakamura, S., Kaziro, Y., Takahashi, T., Takahashi, K. and Nagata, S. (1991) Molecular cloning and expression of a cDNA encoding the secretin receptor. EMBO J., 10: 1635-1641. [PMID:1646711]

10. Jensen, R. T. and Gardner, J. D. (1980) Interaction of cholecystokinin with specific membrane receptors on pancreatic acinar cells. Proc. Natl. Acad. Sci. U.S.A., 77: 2079-2083. [PMID:6246521]

11. Jiang, S. and Ulrich, C. (1995) Molecular cloning and functional expression of a human pancreatic secretin receptor. Biochem. Biophys. Res. Commun., 207: 883-890. [PMID:7864894]

12. Lee, S. M., Chen, L., Chow, B. K. and Yung, W. H. (2005) Endogenous release and multiple actions of secretin in the rat cerebellum. Neuroscience, : -. [PMID:15963647]

13. Mark, H. F. and Chow, B. K. (1995) Localization of the gene encoding the secretin receptor, SCTR, on human chromosome 2q14.1 by fluorescencein situhybridization and chromosome morphometry. Genomics, 29: 817-818. [PMID:8575789]

14. Ng, S. S., Pang, R. T., Chow, B. K. and Cheng, C. H. (1999) Real-time evaluation of human secretin receptor activity using cytosensor microphysiometry. J Cell Biochem, 72: 517-527. [PMID:10022611]

15. Robberecht, P. and Christophe, J. (1988) Secretin receptors in human pancreatic membranes. Pancreas, 3: 529-535. [PMID:3186683]

16. Tay, J., Goulet, M., Rusche, J. and Boismenu, R. (2004) Age-related and regional differences in secretin and secretin receptor mRNA levels in the rat brain. Neurosci Lett, 366: 176-181. [PMID:15276242]

To cite this database page, please use the following:

Dominique Bataille, Philippe Delagrange, Daniel J. Drucker, Burkhard Göke, Rebecca Hills, Kelly E. Mayo, Laurence J. Miller, Bernard Thorens.
Glucagon receptor family: secretin receptor. Last modified on 08/03/2013. Accessed on 19/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=252.


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