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sst2 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
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Gene Expression and Pathophysiology
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 369 17q24 SSTR2 somatostatin receptor 2 155-156
Mouse 7 369 11 E2 Sstr2 somatostatin receptor 2 145,155
Rat 7 369 10q32.1 Sstr2 somatostatin receptor 2 71
Previous and Unofficial Names
SSTR2
SRIF1A
SRIF1
Smstr2
SRIF-1
SS-2-R
SS2-R
SS2R
somatostatin receptor 2
somatostatin receptor subtype 2
somatostatin receptor type 2
somatotropin release-inhibiting factor receptor
SSTR-2
sst2
Smstr-2
Database Links
ChEMBL Target 117 (Hs), 13024 (Mm), 10113 (Rn)
DrugBank Target 6008 (Hs)
Ensembl ENSG00000180616 (Hs), ENSMUSG00000047904 (Mm), ENSRNOG00000002793 (Rn)
Entrez Gene 6752 (Hs), 20606 (Mm), 54305 (Rn)
GeneCards SSTR2 (Hs)
GenitoUrinary Development Molecular Anatomy Project Sstr2 (Mm)
HomoloGene 37427 (Hs)
Human Protein Reference Database 01674 (Hs)
InterPro P30874 (Hs), P30875 (Mm), P30680 (Rn)
KEGG Gene hsa:6752 (Hs), mmu:20606 (Mm), rno:54305 (Rn)
OMIM 182452 (Hs)
PharmGKB Gene PA36155 (Hs)
PhosphoSitePlus P30874 (Hs), P30875 (Mm)
Protein Ontology (PRO) PRO:000001669 (Hs)
RefSeq Nucleotide NM_001050 (Hs), NM_001042606 (Mm), NM_019348 (Rn)
RefSeq Protein NP_001041 (Hs), NP_001036071 (Mm), NP_062221 (Rn)
TreeFam ENSG00000180616 (Hs), ENSMUSG00000047904 (Mm), ENSRNOG00000002793 (Rn)
UniGene Hs. 514451 (Hs)
UniProt P30874 (Hs), P30875 (Mm), P30680 (Rn)
Wikipedia sst2 receptor
Somatostatin receptors
Search for 3D structures on the PDB
Search by keyword: Somatostatin receptors sst2 receptor Search by accession number: P30680, P30874, P30875
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]LTT-SRIF-28 Hs Full agonist 9.9 – 10.0 pKd 125,130-131
[125I]Tyr3 SMS 201-995 Hs Full agonist 9.9 pKd 130,132
[125I]CGP 23996 Hs Full agonist 9.8 pKd 130,132
[125I]MK-678 Mm Full agonist 9.6 pKd 106
[125I]Tyr3 SMS 201-995 Rn Full agonist 9.54 pKd 114
[125I]Tyr10-CST14 Hs Full agonist 9.4 pKd 131-132
[125I]Tyr11-SRIF-14 Mm Full agonist 9.2 pKd 84
[125I]LTT-SRIF-28 Rn Full agonist 9.02 – 9.34 pKd 118-119
[125I]Tyr11-SRIF-14 Rn Full agonist 8.96 pKd 118
L-054,522 Hs Full agonist 11.0 pKi 157
EC 5-21 Hs Full agonist 10.6 pKi 101
NC 8-12 Hs Full agonist 10.6 pKi 101
L-779,976 Hs Full agonist 10.3 pKi 125
SRIF-14 {Sp: Human, Mouse, Rat} Hs Full agonist 8.9 – 10.5 pKi 24,46,101,105,125,130-132,157
DC 23-60 Hs Full agonist 9.6 pKi 101
MK-678 Hs Full agonist 8.8 – 10.3 pKi 24,101,130-132,157
BIM 23023 Hs Full agonist 9.4 pKi 101
BIM 23059 Hs Full agonist 9.4 pKi 101
L-363,377 Hs Full agonist 9.3 pKi 125,157
MK-678 Rn Full agonist 9.3 pKi 93
octreotide Hs Full agonist 8.7 – 9.9 pKi 24,101,130-132,157
SRIF-28 {Sp: Human, Mouse, Rat} Hs Full agonist 8.4 – 10.2 pKi 24,46,101,130-132
SRIF-14 {Sp: Human, Mouse, Rat} Mm Full agonist 8.8 – 9.6 pKi 93
vapreotide Hs Full agonist 8.3 – 10.1 pKi 24,101
BIM 23023 Rn Full agonist 9.2 pKi 93
BIM 23060 Hs Full agonist 9.2 pKi 101
lanreotide Hs Full agonist 8.7 – 9.6 pKi 24,101,130-132
vapreotide Rn Full agonist 9.1 pKi 93
CST-17 {Sp: Human} Hs Full agonist 8.8 – 9.3 pKi 46,131-132
CGP 23996 Hs Full agonist 8.6 – 9.1 pKi 24,130-132
BIM 23068 Hs Full agonist 8.8 pKi 101
lanreotide Rn Full agonist 8.8 pKi 93
SRIF-14 {Sp: Human, Mouse, Rat} Rn Full agonist 8.8 pKi 93
SRIF-28 {Sp: Human, Mouse, Rat} Rn Full agonist 8.8 pKi 93
CST-14 {Sp: Mouse, Rat} Hs Full agonist 8.4 – 9.0 pKi 130-132
octreotide Rn Full agonist 8.7 pKi 93
BIM 23034 Hs Full agonist 8.6 pKi 101
L-362,855 Hs Full agonist 8.4 – 8.8 pKi 130-132
MK-678 Mm Full agonist 7.1 – 9.9 pKi 93
BIM 23052 Hs Full agonist 8.1 – 8.8 pKi 24,130-132
L-363,301 Hs Full agonist 8.3 – 8.5 pKi 131-132
NC 4-28B Hs Full agonist 8.4 pKi 101
octreotide Mm Full agonist 7.5 – 9.2 pKi 93
BIM 23023 Mm Full agonist 7.0 – 9.4 pKi 93
lanreotide Mm Full agonist 6.9 – 9.1 pKi 93
L-362,855 Rn Full agonist 7.9 pKi 93
BIM 23030 Hs Full agonist 7.7 – 7.9 pKi 130-132
L-362,855 Mm Full agonist 7.0 – 8.5 pKi 93
vapreotide Mm Full agonist 6.1 – 9.2 pKi 93
BIM 23056 Hs Full agonist 6.2 – 6.7 pKi 24,130-132
L-779,976 Rn Agonist 10.05 pEC50 87
L-779,976 Rn Partial agonist 9.25 pEC50 87
KE 108 Rn Agonist 7.92 – 10.24 pEC50 34,68
SRIF-14 {Sp: Human, Mouse, Rat} Rn Agonist 9.14 – 8.99 pEC50 87
SOM-230 Rn Agonist 7.76 – 9.07 pEC50 34,68
KE 108 Rn Partial agonist 7.63 pEC50 68
SOM-230 Rn Partial agonist 7.63 pEC50 68
L-363,409 Mm Full agonist 12.0 pIC50 84
BIM 23034 Mm Full agonist 11.7 pIC50 106
BIM 23027 Mm Full agonist 10.2 – 12.0 pIC50 84,106
BIM 23059 Mm Full agonist 11.1 pIC50 106
BIM 23060 Mm Full agonist 10.9 pIC50 106
BIM 23027 Hs Agonist 10.85 pIC50 29
NC 4-28B Mm Full agonist 10.0 – 11.7 pIC50 84,106
BIM 23068 Mm Full agonist 9.8 pIC50 106
BIM 23027 Rn Agonist 9.7 pIC50 65
BIM 23197 Hs Full agonist 9.7 pIC50 128
[Ga-DOTA,Tyr3,Thr8]octreotide Hs Full agonist 9.7 pIC50 8,120
[125I]BIM23027 Rn Full agonist 9.7 pIC50 65
NC 8-12 Mm Full agonist 9.5 pIC50 84
L-363,377 Mm Full agonist 9.4 pIC50 84
[125I][Tyr3,Thr8]octreotide Hs Full agonist 9.33 pIC50 151
SRIF-28 {Sp: Human, Mouse, Rat} Mm Full agonist 9.0 – 9.5 pIC50 93
BOC-ATE Hs Full agonist 9.1 pIC50 55
maltotriose-[125I][Tyr3,Thr8]octreotide Hs Full agonist 9.02 pIC50 151
DC 23-60 Mm Full agonist 9.0 pIC50 106
KE 108 Hs Full agonist 9.0 pIC50 109
SOM-230 Hs Full agonist 9.0 pIC50 127
[125I]Tyr3 SMS 201-995 Hs Full agonist 8.89 pIC50 151
[111In]DOTA-BOC-ATE Hs Full agonist 8.8 pIC50 55
In-NODAGATOC Hs Full agonist 8.77 pIC50 44
Ga-DOTA-NOC Hs Full agonist 8.72 pIC50 8
[111In]DOTA-NOC-ATE Hs Full agonist 8.7 pIC50 55
AM3 Hs Full agonist 8.64 pIC50 49
Ga-DOTA-TOC Hs Full agonist 8.6 pIC50 120
L-363,301 Mm Full agonist 8.1 – 9.1 pIC50 84,106
BIM 23066 Mm Full agonist 8.5 pIC50 106
[111In]DOTA-NOC Hs Full agonist 8.5 pIC50 152
demotate 2 Hs Full agonist 8.49 pIC50 90
NODAGA-[Tyr3]-octreotide Hs Full agonist 8.49 pIC50 44
SiFA-Asn(AcNH-β-Glc)-PEG-Tyr³-octreotate Hs Full agonist 8.48 pIC50 154
[67Ga]NODAGA-[Tyr3]octreotide Hs Full agonist 8.46 pIC50 44
NOC-ATE Hs Full agonist 8.4 pIC50 55
[111In,90Y]DOTA-NOC Hs Full agonist 8.4 pIC50 152
Ga-KE88 Hs Full agonist 8.39 pIC50 56
SiFA-Asn(AcNH-β-Glc)-Tyr³-octreotate Hs Full agonist 8.36 pIC50 154
EC 5-21 Mm Full agonist 8.3 pIC50 106
BIM 23030 Mm Full agonist 8.2 pIC50 106
Y-KE88 Hs Full agonist 8.0 pIC50 56
[111In,90Y]DOTA-TOC Hs Full agonist 7.9 pIC50 152
[111In,90Y]DOTA-OC Hs Full agonist 7.7 pIC50 152
[111In,90Y]DOTA-LAN Hs Full agonist 7.6 pIC50 152
View species-specific agonist tables
Agonist Comments
Liu et al (2005) [1] describe L-779,976 as a full agonist in its ability to inhibit cAMP accumulation, whereas at high concentration it acts as a partial agonist of receptor internalisation (endocytosis). Similarly, SOM-230 and KE 108 have been reported to act as full or partial agonists depending on which outcome of receptor occupation is measured [34,68]. Both ligands exhibit biased agonism: they activate and antagonise distinct signalling pathways [34]. Although SOM-230 and KE 108 potently inhibited cAMP accumulation in sst2A expressing HEK cells, as would be expected of a somatostatin analog, these compounds were also able to antagonise somatostatin induced increase in intracellular calcium and behaved as partial agonists/antagonists for ERK phosphorylation [34].
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[D-Tyr8]CYN 154806 Hs Antagonist 8.1 – 8.9 pKd 100
BASS antagonist Hs Antagonist 9.52 pKi 15
[L-Tyr8]CYN 154806 Hs Antagonist 8.1 – 8.4 pKi 100
PRL-2915 Rn Antagonist 7.9 pKi 64
PRL-2970 Rn Antagonist 7.6 pKi 64
AC-178,335 Rn Antagonist 6.8 pKi 16
KE 108 Rn Antagonist 5.0 pEC50 34
SOM-230 Rn Antagonist 5.0 pEC50 34
analog 31 Hs Antagonist 9.15 pIC50 33
analog 3 Hs Antagonist 9.12 pIC50 33
Ga-NODAGA-LM3 Hs Antagonist 8.89 pIC50 48
DOTA-BASS Hs Antagonist 8.82 pIC50 33
analog 30 Hs Antagonist 8.77 pIC50 33
BIM 23627 Hs Antagonist 8.2 pIC50 144
BIM 23454 Hs Antagonist 7.5 pIC50 144
View species-specific antagonist tables

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

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G protein independent mechanism
G protein (identity unknown) 		Adenylate cyclase inhibition
Potassium channel
Calcium channel
Other - See Comments
Comments:  G protein independent: Inhibition of phosphoinositide 3-kinase activity through direct molecular interactions (and competition) between sst2 first intracellular loop and the regulatory PI3K p85 subunit or filamin-A [20,98].
G-protein-dependent: activation of ERK and PI3K activity in sst2-transfected CHO cells [76] and [60].
Other: Inhibition of L and N voltage gated Ca2++ channels activity [158].
References:  66,69,80,129
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G protein independent mechanism
G protein (identity unknown) 		Adenylate cyclase stimulation
Phospholipase C stimulation
Potassium channel
Calcium channel
Phospholipase D stimulation
Other - See Comments
Comments:  PLC activation is via the Gq G-protein.
K+ channel activation and Ca2+ channel inhibition is via Gi/Go.
There is also protein tyrosine phosphatase (PTP) activation via a PTX-insensitive G-protein.
sst2 activates PLC via a mechanism involving Galpha14 and has also been shown to activate PLD in clonal beta cells HIT-T15 [36,63,85].
Adenylate cyclase stimulation has been reported at very high agonist doses in overexpression systems.
Other downstream events reported to be consequential to somatostatin binding include inhibition of the PI3K-mTOR pathway and cap-dependent translation [12,31,141], activation of the protein-tyrosine phosphatases SHP-1, SHP-2 or PTPeta [14,50] and inhibition of eNOS activity [9].
References:  5,9,12,14,25,31,36,41,50,63,73,80,85,107,140-141
Tissue Distribution
A and B pancreatic islet cells, but not in adjacent acinar cells.
Species:  Human
Technique:  Immunohistochemistry, autoradiography
References:  111
Pancreatic islets: co-localised with glucagon in alpha-cells.
Species:  Human
Technique:  immunocytochemistry.
References:  74
Lymphoid cells.
Species:  Human
Technique:  RT-PCR.
References:  143
Peritumoral veins of human tumours.
Species:  Human
Technique:  Radioligand binding.
References:  42
Proliferating endothelium.
Species:  Human
Technique:  Immunocytochemistry.
References:  4
Thymocytes.
Species:  Human
Technique:  RT-PCR.
References:  52
Spleen.
Species:  Human
Technique:  Immunohistochemistry.
References:  51
Pancreatic exocrine tissue and pancreatic ductal adenocarcinoma.
Species:  Human
Technique:  Immunohistochemistry, RT-PCR
References:  26,77,142
GI tract (gastrointestinal lymphatic and nervous components, but not in gastrointestinal circular and longitudinal smooth muscle).
Species:  Human
Technique:  Immunohistochemistry.
References:  58,112
Lymphoid tissue, plexus.
Species:  Human
Technique:  Immunohistochemistry, autoradiography.
References:  112
Brain.
Species:  Human
Technique:  Autoradiography.
References:  115
Vessels.
Species:  Human
Technique:  Autoradiography.
References:  42,113,116
Kidney.
Species:  Human
Technique:  Autoradiography.
References:  110
Lymphoid tissue.
Species:  Human
Technique:  Autoradiography, in vivo scintigraphy
References:  117,122
Macrophages.
Species:  Human
Technique:  RT-PCR.
References:  10
Pituitary.
Species:  Human
Technique:  RT-PCR.
References:  95
High levels in the cerebrum and kidney. Low levels in the jejunum, colon and liver.
Species:  Mouse
Technique:  RNA blotting.
References:  155
Cortex, amygdala, claustrum, endopiriform nucleus, arcuate and periventricular nuclei of the hypothalamus, medial habenular nucleus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  21
Parietal cells and ECL cells in stomach, and myenteric neurons.
Species:  Mouse
Technique:  Immunohistochemistry and LacZ knock-in.
References:  7
Hippocampus and many other brain areas.
Species:  Rat
Technique:  Immunohistochemistry.
References:  43
Pituitary.
Species:  Rat
Technique:  RT-PCR.
References:  39,47
Pituitary: somatotrophs (GH release), thyrotrophs (TSH release), lactotrophs (PRL release), as well as gonadotrophs and corticotrophs.
Species:  Rat
Technique:  double label in situ hybridisation.
References:  39
Pancreas.
Species:  Rat
Technique:  Immunohistochemistry.
References:  67,138
Fundic gastric mucosa of the stomach.
Species:  Rat
Technique:  RT-PCR.
References:  81
Aorta.
Species:  Rat
Technique:  RT-PCR and immunocytochemistry.
References:  70
Adrenal gland.
Species:  Rat
Technique:  Autoradiography.
References:  92
Hypothalamus: Medial preoptic area, suprachiasmatic nucleus, arcuate nucleus, anterior hypothalamic nucleus, ventromedial and dorsomedial nuclei, medial tuberal nucleus.
Species:  Rat
Technique:  in situ hybridisation.
References:  17
Anterior pituitary.
Species:  Rat
Technique:  Immunohistochemistry.
References:  94
High levels in the amygdala, cortex, hypothalamus and hippocampus. Medium levels in the striatum, midbrain, thalamus, cerebellum and spinal cord.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  23
Pituitary, spleen and pancreas.
Species:  Rat
Technique:  Nuclease protection analysis.
References:  23
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
Receptor internalisation.
Species:  Rat
Tissue:  Pituitary
Response measured:  Receptor endocytosis.
References:  62
Measurement of GH release in in vivo rat studies.
Species:  Rat
Tissue:  In vivo.
Response measured:  Reduction in circulating GH.
References:  157
Measurement of GH release from rat anterior pituitary.
Species:  Rat
Tissue:  Rat anterior pituitary.
Response measured:  Inhibition of GH release.
References:  106
Measurement of CAMP accumulation in CHO cells stably transfected with human sst2 receptors.
Species:  Human
Tissue:  CHO cells expressing the luciferase reporter gene under the control of the serum response element, expressing recombinant human sst2 receptors.
Response measured:  Inhibition of cAMP accumulation.
References:  99
Measurement of agonist-driven luciferase expression in CHO cells stably transfected with human sst2 receptors.
Species:  Human
Tissue:  CHO cells expressing the luciferase reporter gene under the control of the serum response element, expressing recombinant sst2 receptors.
Response measured:  Inhibition of agonist-driven expression of the luciferase reporter gene.
References:  99
Measurement of the cAMP and Ca2+ levels in GC cells (growth cells) from a rat somatotroph tumour treated with the sst2 selective agonist L-779,976.
Species:  Rat
Tissue:  GC cells (growth cells) from a rat somatotroph tumour endogenously expressing all 5 SRIF receptors.
Response measured:  Inhibition of basal cAMP and Ca2+ levels.
References:  32
Measurement of GH release from GC cells (growth cells) from a rat somatotroph tumour treated with the sst2 selective agonist L-779,976.
Species:  Rat
Tissue:  GC cells (growth cells) from a rat somatotroph tumour endogenously expressing all 5 sst receptors.
Response measured:  Reduction in GH secretion.
References:  32
Measurement of GH release from primary cultures of rat anterior pituitary cells.
Species:  Rat
Tissue:  primary cultures of rat anterior pituitary cells.
Response measured:  Inhibition of GH release.
References:  157
Measurement of protein tyrosine phosphatase, MAPK and AP-1 activity in human U343 glioma cells expressing only sst2.
Species:  Human
Tissue:  human U343 glioma cells.
Response measured:  Activation of the protein tyrosine phosphatase SHP2, dephosphorylation of MAPK and inhibition of AP-1 activation.
References:  61
Measurement of GH, TSH and PRL secretion in primary human fetal pituitary cells, when treated with a sst2 selective agonist.
Species:  Human
Tissue:  Primary human fetal pituitary cells.
Response measured:  Reduction of GH, TSH and PRL secretion.
References:  128
Measurement of protein tyrosine phosphatase activity in the S49 cell line derived from a murine T cell lymphoma.
Species:  Mouse
Tissue:  S49 cells
Response measured:  Stimulation of protein tyrosine phosphatase activity.
References:  41
Measurement of cAMP accumulation in HEK 293 cells stably transfected with human sst2 receptors.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  69
Measurement of Ca2+ current in AtT-20 cells expressing sst2 receptors.
Species:  Mouse
Tissue:  AtT-20 cell line (mouse anterior pituitary).
Response measured:  Coupling to L-type Ca2+ current.
References:  140
Measurement of AC activity (cAMP levels) in CCL39 cells stably transfected with human sst2 receptors.
Species:  Human
Tissue:  CCL39 cells.
Response measured:  Inhibition of AC activity.
References:  129
Measurement of ECAR (extracellular acidification rate) in F4C1 cells stably transfected with mouse sst2 receptors.
Species:  Mouse
Tissue:  F4C1 cells (rat pituitary).
Response measured:  Acute increase in ECAR, followed by decrease.
References:  35
Measurement of GIRK currents (inward potassium currents) in Xenopus oocyte cells stably transfected with rat sst2 receptors and GIRK1 channels.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  Activation of GIRK current.
References:  73
Measurement of AMPA/Kainate receptor activation in mouse hypothalamic neurons expressing sst2 receptors.
Species:  Mouse
Tissue:  Hypothalamic neurons grown in primary cell culture.
Response measured:  Decrease in AMPA/Kainate receptor-mediated response to glutamate.
References:  78
Measurement of PLC activity and cytosolic Ca2+ levels in COS-7 cells stably transfected with human sst2 receptors.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Activation of PLC and Ca2+ mobilisation.
References:  5
Measurement of NOS activity (NO production) in CHO-K1 cells stably transfected with rat sst2 receptors.
Species:  Rat
Tissue:  CHO-K1 cells.
Response measured:  Inhibition of NO production.
References:  9
In vivo agonist-induced internalisation of sst2 receptors in somatostatin target tissues.
Species:  Rat
Tissue:  AR42J tumour model in rat.
Response measured:  The sst2 receptors in treated animals are detected intracellularly after agonist treatment.
References:  150
Receptor internalisation.
Species:  Rat
Tissue:  Pancreatic acinar cells
Response measured:  Receptor endocytosis.
References:  45
Receptor phosphorylation.
Species:  Rat
Tissue:  CHO (Chinese Hamster Ovary) cells
Response measured:  Site specific sst2A phosphorylation.
References:  54,86
Receptor phosphorylation.
Species:  Rat
Tissue:  Pituitary
Response measured:  Receptor phosphorylation.
References:  62
Receptor phosphorylation.
Species:  Human
Tissue:  Neuroendocrine tumours
Response measured:  Receptor phosphorylation.
References:  88
Internalisation of sst2 in neuroendocrine tumour cells of patients treated with octreotide determined by IHC.
Species:  Human
Tissue:  Neuroendocrine tumours (pancreatic, bronchial, bile duct).
Response measured:  Sst2 receptors can be internalised in sst2-expressing neuroendocrine tumors in patients under octreotide therapy.
References:  121
Physiological Functions
Inhibition of GH release (synergistic with sst5).
Species:  Human
Tissue:  Primary fetal pituitary cell culture.
References:  108
Inhibition of gastric acid secretion.
Species:  Mouse
Tissue:  Stomach.
References:  91,103
Inhibition of histamine release leading to inhibition of gastric acid release.
Species:  Mouse
Tissue:  Stomach.
References:  72
Inhibition of glucagon release.
Species:  Mouse
Tissue:  Pancreas.
References:  137
Control of dopamine and glutamate release in the striatum.
Species:  Mouse
Tissue:  Striatum.
References:  6
Stimulation of ductile bile absorption and inhibition of ductile bile secretion.
Species:  Mouse
Tissue:  Cholangiocytes.
References:  57
Inhibition of peristalsis in the jejunum.
Species:  Mouse
Tissue:  Jejunum.
References:  2
Inhibition of peristalsis in the jejunum.
Species:  Rat
Tissue:  Jejunum.
References:  2
Lymphocyte activation, development and tumorgenesis.
Species:  Human
Tissue:  Lymphatic cells.
References:  143
Decrease in AMPA/Kainate receptor-mediated responses to glutamate.
Species:  Mouse
Tissue:  Hypothalamic neurones grown in primary cell culture.
References:  78
Inhibition of GH release (with sst3).
Species:  Rat
Tissue:  Hepatocytes (liver cells).
References:  97
Inhibition of glucagon release.
Species:  Rat
Tissue:  Batch incubations of isolated rat islets, perifused isolated rat islets, and isolated perfused rat pancreas.
References:  30
Positive regulation of neuronal migration during brain development, inhibition of keratinocyte migration and delay in epidermal wound healing
Species:  Human
Tissue:  Brain, epidermis.
References:  82,149
Inhibition of insulin and glucagon secretion.
Species:  Human
Tissue:  Isolated human pancreatic islet cells.
References:  133
Positive regulation of food intake, grooming behaviour and rectal temperature.
Species:  Rat
Tissue:  Brain.
References:  136
Anxiolytic effects in both the amygdala and the septum.
Species:  Rat
Tissue:  Brain.
References:  159
Inhibition of cell proliferation in vivo.
Species:  Rat
Tissue:  Glioma.
References:  13
Inhibition of cell proliferation and/or induction of cell apoptosis in vitro and in vivo.
Species:  Human
Tissue:  Endothelial cells, fibroblasts, lymphocytes, normal and tumor epithelial, neuroendocrine and pituitary cells.
References:  3,53,59,75,79,124,139,153
Modulation of in vivo gamma oscillation and odor discrimination.
Species:  Mouse
Tissue:  Olfactory bulb.
References:  83
Physiological Consequences of Altering Gene Expression
Mice lacking in the sst2 receptor in the retina show a reduction in size of rod bipolar cell (RBC) axonal endings, up-regulation of the sst1 receptor at/near the eye opening, and a decrease in SRIF levels.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
Mice with the sst2 gene removed show a normal level of locomotion and coordination but severe impairment in beam-walking, a test for fine motor control.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  6
Mice lacking the sst2 receptor show a reduction in the inhibition of glucagon release by somatostatin, but no change in the inhibition of insulin secretion, from mouse pancreatic islets. This suggests the involvement of the sst2 receptor in the inhibition of glucagon secretion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  137
Mice lacking the sst2 receptor show no change in either basal acid secretion or secretion in response to meal, despite the inhibition of gastric acid being shown to be mediated through sst2 receptors. This lack of inhibition via SRIF is not compensated for by other somatostatin receptor subtypes, and so must be via a somatostatin-independent mechanism.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  103
The migrating motor complexes in the jejunum of rats, mice and sst2 receptor knock-out mice were studied, and the result was that there is a non-sst2 receptor mediated inhibition of peristalsis in the knock-out mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  2
Studies involving sst2 knock-out mice show that the GH-mediated negative feedback loop on GHRH neurons involves the sst2 receptor.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  160
Studies involving sst2 receptor and glycoprotein hormone α-subunit knock-out mice (Sstr2-/-,αGsu-/-) develop hyperplasia of thyrotropes. Sst2 receptors are shown not to be required in the feedback loop regulating TSH secretion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  22
Studies using sst2 receptor knock-out mice show an involvement of the sst2 receptor in modulating locomotor, exploratory and emotional reactivity in mice. They showed an increased release of ACTH (a regulator of the stress response) from the pituitary.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  148
Mice lacking the sst2 receptor show decreased susceptibility to kainate-induced seizures suggesting that sst2 receptors in mice do not mediate direct inhibitory actions of somatostatin on neuronal excitability.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  96
Mice lacking the sst2 receptor subtype showed lower gastric pH values and no change in gastrin levels, suggesting that sst2 in wild-type mice is inhibiting gastric acid secretion by inhibiting the actions of gastrin.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  91
Mice with sst2 knockout are more sensitive than wild-type to hypoxia-induced neovascularization in the retina.
Species:  Mouse
Tissue:  Retina
Technique:  Knockout (homologous recombination).
References:  38
sst2 decreases cell viability and hormonal hypersecretion and reverses octreotide resistance of human pituitary adenomas and exhibits a tumour suppressive function and sensitisation to octreotide.
Species:  Human
Tissue:  Primary cultures of human pituitary adenomas.
Technique:  Gene over-expression.
References:  3
Overexpression of sst2 in human pancreatic cancer cells inhibits tumour growth, angiogenesis and metastasis, and induces apoptosis resulting in a tumour suppressive function.
Species:  Human
Tissue:  Exocrine pancreatic cancer cells.
Technique:  Gene over-expression.
References:  18,27,40,59,77,124,146
Mice with sst2 knockout under diet-induced obesity have hyperglycemia, nonfasting hyperglucagonemia and decreased hepatic glycogen deposition (hyperglucagonemia).
Species:  Mouse
Tissue:  Pancreas, liver.
Technique:  Gene knock-outs.
References:  134
Increased anxiety-related behaviour in a number of behavioural paradigms, while locomotor and exploratory activity was decreased in stress-inducing situations.
Species:  Mouse
Tissue:  Neurons.
Technique:  Gene knock-outs.
References:  148
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
B6.129P2-Sstr2		 MGI:98328  MP:0004924 abnormal behavior PMID: 12752788 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
involves: 129P2/OlaHsd * C57BL/6		 MGI:98328  MP:0004994 abnormal brain wave pattern PMID: 15548214 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
involves: 129S4/SvJae		 MGI:98328  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 17425570 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
B6.129P2-Sstr2		 MGI:98328  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 14750962 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
B6.129P2-Sstr2		 MGI:98328  MP:0004494 abnormal synaptic glutamate release PMID: 12752788 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
B6.129P2-Sstr2		 MGI:98328  MP:0005643 decreased dopamine level PMID: 12752788 
Sstr2tm1Rgs Sstr2tm1Rgs/Sstr2tm1Rgs
involves: 129S7/SvEvBrd * C57BL/6		 MGI:98328  MP:0001417 decreased exploration in new environment PMID: 11029646 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
B6.129P2-Sstr2		 MGI:98328  MP:0003038 decreased infarction size PMID: 15601946 
Sstr2tm1Rgs Sstr2tm1Rgs/Sstr2tm1Rgs
involves: 129S7/SvEvBrd * C57BL/6		 MGI:98328  MP:0002757 decreased vertical activity PMID: 11029646 
Sstr2tm1Rgs Sstr2tm1Rgs/Sstr2tm1Rgs
involves: 129S7/SvEvBrd * C57BL/6		 MGI:98328  MP:0001402 hypoactivity PMID: 11029646 
Sstr2tm1Pce Sstr2tm1Pce/Sstr2tm1Pce
B6.129P2-Sstr2		 MGI:98328  MP:0001405 impaired coordination PMID: 12752788 
Sstr2tm1Rgs Sstr2tm1Rgs/Sstr2tm1Rgs
involves: 129S7/SvEvBrd * C57BL/6		 MGI:98328  MP:0001363 increased anxiety-related response PMID: 11029646 
Sstr2tm1Rgs Sstr2tm1Rgs/Sstr2tm1Rgs
involves: 129S7/SvEvBrd * C57BL/6		 MGI:98328  MP:0001748 increased circulating adrenocorticotropin level PMID: 11029646 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Insulinoma.
Role:  Octreotide efficacy on hypoglycemia in insulinoma patients correlates with positive anti-sst2A immunostaining.
References:  147
Mutations not determined
Disease:  Metastatic midgut neuroendocrine tumours (NET)
Role:  The randomized, placebo-controlled, prospective PROMID (placebo-controlled, double-blind, prospective randomized study) showed effect of octreotide LAR in the control of tumour growth in patients with metastatic midgut NET.
References:  123
Mutations not determined
Disease:  Endocrine tumours.
Role:  Indium-111-pentetreotide scintigraphy and somatostatin receptor expression are new prognosis factors for malignant well-differentiated endocrine tumours.
References:  11
Mutations not determined
Gene Expression and Pathophysiology
SST2 mRNA levels are lower in subjects with schizophrenia.
Tissue or cell type:  Dorsolateral prefrontal cortex (DLPFC).
Pathophysiology:  Schizophrenia.
Species:  Human
Technique:  In-situ hybridisation.
References:  19
Loss of somatostatin receptor 2 confers resistance to octreotide in GH secreting adenomas
Tissue or cell type:  Surgically removed somatotroph tumour tissue.
Pathophysiology:  Octeotride resistant acromegaly.
Species:  None
Technique:  Immunocytochemistry.
References:  104
Biologically Significant Variants
Existence of a splice variant, sst2(b), lacking around 23 amino acid residues and differing in 15 amino acids at the C-terminus. The mRNA of this splice variant is more abundant in mouse tissues than the unspliced form, sst2(a).
Type:  Splice variant.
Species:  Mouse
References:  145
Existence of the splice variant sst2(b) in the rat stomach. Expression of the spliced and unspliced (sst2(a)) receptors in CHO-K1 cells shows minimal differences in the operational characteristics of the receptor.
Type:  Splice variant.
Species:  Rat
References:  126
Sequence analysis of the human SSTR2 gene shows conserved intron/exon boundaries and amino acid sequence between it and the murine Sstr2 genes, suggesting that the human SSTR2 gene is also capable of generating splice variants.
Type:  Splice variant.
Species:  Human
References:  102
A genome-wide association study identified the rs1466113 polymorphism (G>C) in the SSTR2 and associates this with obesity and food intake in a Mediterranean population and describes this as one of the polymorphisms most significantly associated with body mass index (BMI).
Type:  Naturally occurring SNPs.
Species:  Human
References:  135
General Comments
The sst2 receptor can be targeted by somatostatin analogues to inhibit hormone secretion for pituitary tumors and GEP-NET [37]. The receptor can also be targeted for nuclear imaging and radionuclide treatment [89].

REFERENCES

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To cite this database page, please use the following:

Stefan Schulz, Corinne Bosquet, Justo Castano, Micheal Culler, Jacques Epelbaum, Leo Hofland, Daniel Hoyer, Jean-Claude Reubi, Herbert Schmid, Agnes Schonbrunn.
Somatostatin receptors: sst2 receptor. Last modified on 11/03/2013. Accessed on 22/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=356.


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