Nomenclature: sst4 receptor

Family: Somatostatin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

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
SSTR5
SSTR4
SRIF2
SRIF2B
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
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
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]Tyr10-CST14 Hs Full agonist 9.4 pKd 36
pKd 9.4 [36]
[125I]CGP 23996 Hs Full agonist 9.4 pKd 36
pKd 9.4 [36]
[125I]Tyr11-SRIF-14 Hs Full agonist 9.0 pKd 30
pKd 9.0 [30]
[125I]LTT-SRIF-28 Hs Full agonist 8.4 pKd 31
pKd 8.4 [31]
β3-tetrapeptide Hs Full agonist 7.3 – 7.8 pKd 24
pKd 7.3 – 7.8 [24]
β3-tetrapeptide Mm Full agonist 7.2 – 7.5 pKd 24
pKd 7.2 – 7.5 [24]
L-803,087 Hs Full agonist 9.2 pKi 31
pKi 9.2 [31]
CST-17 {Sp: Human} Hs Full agonist 8.5 – 9.6 pKi 35-36
pKi 8.5 – 9.6 [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
pKi 8.4 – 9.3 [4,9,22,26-27,31,35-36,40]
CGP 23996 Hs Full agonist 8.6 – 8.8 pKi 35-36
pKi 8.6 – 8.8 [35-36]
CST-14 {Sp: Mouse, Rat} Hs Full agonist 8.6 – 8.8 pKi 35-36
pKi 8.6 – 8.8 [35-36]
SRIF-28 {Sp: Human, Mouse, Rat} Hs Full agonist 8.1 – 9.2 pKi 4,9,22,26,35-36
pKi 8.1 – 9.2 [4,9,22,26,35-36]
BIM 23295 Hs Full agonist 8.5 pKi 22
pKi 8.5 [22]
BIM 23052 Hs Full agonist 8.2 – 8.6 pKi 35
pKi 8.2 – 8.6 [35]
NNC269100 Hs Full agonist 8.2 pKi 21
pKi 8.2 (Ki 6x10-9 M) [21]
BIM 23068 Hs Full agonist 8.0 pKi 26
pKi 8.0 [26]
L-362,855 Hs Full agonist 6.8 – 7.3 pKi 35-36
pKi 6.8 – 7.3 [35-36]
[125I]LTT-SRIF-28 Hs Full agonist 9.6 pIC50 35
pIC50 9.6 [35]
KE 108 Hs Full agonist 8.8 pIC50 28
pIC50 8.8 [28]
Des-AA5-[D-Trp8]SRIF Hs Full agonist 8.7 – 8.9 pIC50 11
pIC50 8.7 – 8.9 [11]
H-c[DCys-Phe-LAgl(NβMe,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH Hs Full agonist 8.5 pIC50 29
pIC50 8.5 [29]
H-c[Cys-Phe-LAgl(NβMe,benzoyl)-Trp-Lys-Thr-Phe-Cys]-OH Hs Full agonist 8.1 – 8.6 pIC50 29
pIC50 8.1 – 8.6 [29]
H-c[Cys-Phe-LAgl(NβMe,benzoyl)-DTrp-Lys-Thr-Phe-Cys]-OH Hs Full agonist 8.3 pIC50 29
pIC50 8.3 [29]
SRIF-14 {Sp: Human, Mouse, Rat} Rn Full agonist 8.2 pIC50 38
pIC50 8.2 [38]
BIM 23052 Rn Full agonist 8.1 pIC50 38
pIC50 8.1 [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
pKi 6.2 – 6.5 [25]
PRL-2915 Hs Antagonist 6.0 pKi 13
pKi 6.0 [13]
[D-Tyr8]CYN 154806 Hs Antagonist 5.8 – 6.0 pKi 25
pKi 5.8 – 6.0 [25]
BIM 23454 Hs Antagonist 6.5 pIC50 37
pIC50 6.5 [37]
BIM 23627 Hs Antagonist 6.4 pIC50 37
pIC50 6.4 [37]
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
Poorly expressed in pancreatic islet cells, only in beta-cells.
Species:  Human
Technique:  immunocytochemistry.
References:  17
Blood vessels.
Species:  Human
Technique:  PCR.
References:  6
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
Whole placenta and cytotrophoblast cells.
Species:  Human
Technique:  RT-PCR.
References:  5
Brain and lung tissue.
Species:  Human
Technique:  Northern blotting.
References:  30
Aorta.
Species:  Rat
Technique:  RT-PCR and immunocytochemistry.
References:  15
Spleen, heart, kidney.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  3
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
Pituitary.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  3
Fundic gastric mucosa of the stomach.
Species:  Rat
Technique:  RT-PCR.
References:  19
Expression Datasets

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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

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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 
Available Assays
DiscoveRx PathHunter® CHO-K1 SSTR4 β-Arrestin Cell Line (Cat no. 93-0308C2)
PathHunter® eXpress SSTR4 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0308E2CP2M)
more info

REFERENCES

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25. Nunn C, Schoeffter P, Langenegger D, Hoyer D. (2003) Functional characterisation of the putative somatostatin sst2 receptor antagonist CYN 154806. Naunyn Schmiedebergs Arch Pharmacol367: 1-9. [PMID:12616335]

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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 29/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=358.

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