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sst4 receptor

Family: Somatostatin receptors

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
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 388 20p11.2 SSTR4 somatostatin receptor 4 8,30,39,41
Mouse 7 384 2 G3 Sstr4 somatostatin receptor 4 33
Rat 7 384 3q41 Sstr4 somatostatin receptor 4 2
Previous and Unofficial Names
SSTR4
SSTR5
SRIF2B
SRIF2
Smstr4
SS-4-R
SS4-R
SS4R
Somatostatin receptor subtype 4 Rattus norvegicus Sprague-Dawley major hippocampal somatostatin receptor (SSTR4) mRNA
somatostatin receptor 4
somatostatin receptor type 4
sst4
Database Links
ChEMBL Target 10183 (Hs), 11895 (Mm), 11264 (Rn)
Ensembl ENSG00000132671 (Hs), ENSMUSG00000037014 (Mm), ENSRNOG00000004641 (Rn)
Entrez Gene 6754 (Hs), 20608 (Mm), 25555 (Rn)
GeneCards SSTR4 (Hs)
GenitoUrinary Development Molecular Anatomy Project Sstr4 (Mm)
HomoloGene 20286 (Hs)
Human Protein Reference Database 01676 (Hs)
InterPro P31391 (Hs), P49660 (Mm), P30937 (Rn)
KEGG Gene hsa:6754 (Hs), mmu:20608 (Mm), rno:25555 (Rn)
OMIM 182454 (Hs)
PharmGKB Gene PA36157 (Hs)
PhosphoSitePlus P31391 (Hs), P49660 (Mm), P30937 (Rn)
Protein Ontology (PRO) PRO:000001671 (Hs)
RefSeq Nucleotide NM_001052 (Hs), NM_009219 (Mm), NM_013036 (Rn)
RefSeq Protein NP_001043 (Hs), NP_033245 (Mm), NP_037168 (Rn)
TreeFam ENSG00000132671 (Hs), ENSMUSG00000037014 (Mm), ENSRNOG00000004641 (Rn)
UniGene Hs. 532687 (Hs)
UniProt P31391 (Hs), P49660 (Mm), P30937 (Rn)
Wikipedia sst4 receptor
Somatostatin receptors
Search for 3D structures on the PDB
Search by keyword: Somatostatin receptors sst4 receptor Search by accession number: P30937, P31391, P49660
Natural/Endogenous Ligand(s)
CST-14 {Sp: Mouse, Rat}
CST-17 {Sp: Human}
SRIF-14 {Sp: Human, Mouse, Rat}
SRIF-28 {Sp: Human, Mouse, Rat}
Comments: SRIF-14 and SRIF-28 are the active fragments of precursor somatostatin
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]CGP 23996 Hs Full agonist 9.4 pKd 36
[125I]Tyr10-CST14 Hs Full agonist 9.4 pKd 36
[125I]Tyr11-SRIF-14 Hs Full agonist 9.0 pKd 30
[125I]LTT-SRIF-28 Hs Full agonist 8.4 pKd 31
β3-tetrapeptide Hs Full agonist 7.3 – 7.8 pKd 24
β3-tetrapeptide Mm Full agonist 7.2 – 7.5 pKd 24
L-803,087 Hs Full agonist 9.2 pKi 31
CST-17 {Sp: Human} Hs Full agonist 8.5 – 9.6 pKi 35-36
SRIF-14 {Sp: Human, Mouse, Rat} Hs Full agonist 8.4 – 9.3 pKi 4,9,22,26-27,31,35-36,40
CGP 23996 Hs Full agonist 8.6 – 8.8 pKi 35-36
CST-14 {Sp: Mouse, Rat} Hs Full agonist 8.6 – 8.8 pKi 35-36
SRIF-28 {Sp: Human, Mouse, Rat} Hs Full agonist 8.1 – 9.2 pKi 4,9,22,26,35-36
BIM 23295 Hs Full agonist 8.5 pKi 22
BIM 23052 Hs Full agonist 8.2 – 8.6 pKi 35
NNC269100 Hs Full agonist 8.2 pKi 21
BIM 23068 Hs Full agonist 8.0 pKi 26
L-362,855 Hs Full agonist 6.8 – 7.3 pKi 35-36
[125I]LTT-SRIF-28 Hs Full agonist 9.6 pIC50 35
KE 108 Hs Full agonist 8.8 pIC50 28
Des-AA5-[D-Trp8]SRIF Hs Full agonist 8.7 – 8.9 pIC50 11
H-c[DCys-Phe-LAgl(NβMe,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH Hs Full agonist 8.5 pIC50 29
H-c[Cys-Phe-LAgl(NβMe,benzoyl)-Trp-Lys-Thr-Phe-Cys]-OH Hs Full agonist 8.1 – 8.6 pIC50 29
H-c[Cys-Phe-LAgl(NβMe,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH Hs Full agonist 8.3 pIC50 29
SRIF-14 {Sp: Human, Mouse, Rat} Rn Full agonist 8.2 pIC50 38
BIM 23052 Rn Full agonist 8.1 pIC50 38
View species-specific agonist tables
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[L-Tyr8]CYN 154806 Hs Antagonist 6.2 – 6.5 pKi 25
PRL-2915 Hs Antagonist 6.0 pKi 13
[D-Tyr8]CYN 154806 Hs Antagonist 5.8 – 6.0 pKi 25
BIM 23454 Hs Antagonist 6.5 pIC50 37
BIM 23627 Hs Antagonist 6.4 pIC50 37

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  1,14,34
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G protein (identity unknown) 		Potassium channel
Calcium channel
Other - See Comments
Comments:  Activation of K+ channels and inhibition of Ca2+ channels is via Gi/Go G-proteins. Protein tyrosine phosphatase (PTP), Na+/H+ exchanger (NHE1), MAPK cascade and PLA2 activation are via unknown G-proteins.
References:  1,12,16,18,20
Tissue Distribution
Whole placenta and cytotrophoblast cells.
Species:  Human
Technique:  RT-PCR.
References:  5
Blood vessels.
Species:  Human
Technique:  PCR.
References:  6
Poorly expressed in pancreatic islet cells, only in beta-cells.
Species:  Human
Technique:  immunocytochemistry.
References:  17
Hippocampus (CA4 subfield pyramidal cells, granule cells in the dendate gyrus), frontal cortex (pyramidal cells), cerebellum.
Species:  Human
Technique:  RT-PCR and in situ hybridisation.
References:  32
Brain and lung tissue.
Species:  Human
Technique:  Northern blotting.
References:  30
Pituitary.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  3
Spleen, heart, kidney.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  3
Fundic gastric mucosa of the stomach.
Species:  Rat
Technique:  RT-PCR.
References:  19
Aorta.
Species:  Rat
Technique:  RT-PCR and immunocytochemistry.
References:  15
Medium levels in the hippocampus, amygdala, olfactory bulb, cortex, preoptic area.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  3
Pituitary.
Species:  Rat
Technique:  RT-PCR.
References:  7,10
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 accumulation (AC activity) in BHK cells stably transfected with human sst4 receptors.
Species:  Human
Tissue:  BHK cells.
Response measured:  Inhibition of cAMP accumulation.
References:  21
Measurement of NHE1 (Na-H exchanger) activity (pH recovery) in Ltk- cells stably expressing rat sst4 receptors.
Species:  Rat
Tissue:  Mouse fibroblast Ltk- cells.
Response measured:  Inhibition of NHE1 activity.
References:  20
Measurement of protein tyrosine phosphatase activity and cell proliferation in PC C13 thyroid cells.
Species:  Rat
Tissue:  PC C13 thyroid cells line.
Response measured:  Stimulation of protein tyrosine phosphatase activity and subsequent inhibition of cell proliferation.
References:  12
Measurement of cAMP accumulation (AC activity) in HEK 293 cells stably transfected with human sst4 receptors.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  14
Measurement of AC activity (cAMP levels) in CCL39 cells stably transfected with human sst4 receptors.
Species:  Human
Tissue:  CCL39 cells.
Response measured:  Inhibition of AC activity.
References:  34
Measurement of GIRK currents (inward potassium currents) in Xenopus oocyte cells stably transfected with rat sst4 and GIRK1 channels.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  Activation of GIRK current.
References:  16
Measurement of AC activity, arachidonate release (PLA2 activity), intracellular Ca2+ levels and MAPK activity in CHO-K1 cells stably transfected with rat sst4 receptors.
Species:  Rat
Tissue:  CHO-K1 cells.
Response measured:  Inhibition of AC activity, stimulation of arachidonate release (PLA2 activation), no change in Ca2+ mobilisation, and activation of MAPK cascade.
References:  1
Physiological Functions
Antiproliferation.
Species:  Rat
Tissue:  PC C13 clonal thyroid cell line.
References:  12
Enhancement of AMPA receptor-mediated currents in the hippocampus, and suggested interaction with the sst2 receptor.
Species:  Mouse
Tissue:  Hippocampus.
References:  23
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0002441 abnormal granulocyte morphology PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0002463 abnormal neutrophil physiology PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0001785 edema PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0005407 hyperalgesia PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0001952 increased airway responsiveness PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0008566 increased interferon-gamma secretion PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0008657 increased interleukin-1 beta secretion PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0005617 increased susceptibility to type IV hypersensitivity reaction PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0008560 increased tumor necrosis factor secretion PMID: 19622729 
Sstr4tm1Szo Sstr4tm1Szo/Sstr4tm1Szo
B6.129P2-Sstr4		 MGI:105372  MP:0003828 pulmonary edema PMID: 19622729 

REFERENCES

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To cite this database page, please use the following:

Jacques Epelbaum, Wasyl Feniuk, Anthony Harmar, Rebecca Hills, Daniel Hoyer, Patrick P. A. Humphrey, Wolfgang Meyerhof, Anne-Marie O'Carroll, Yogesh C. Patel, Terry Reisine, Jean-Claude Reubi, Marcus Schindler, Agnes Schonbrunn, John E. Taylor, Annamaria Vezzani.
Somatostatin receptors: sst4 receptor. Last modified on 11/03/2013. Accessed on 19/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=358.


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