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SST2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 356

Nomenclature: SST2 receptor

Family: Somatostatin receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 369 17q25.1 SSTR2 somatostatin receptor 2 159-160
Mouse 7 369 11 79.05 cM Sstr2 somatostatin receptor 2 149,159
Rat 7 369 10q32.1 Sstr2 somatostatin receptor 2 69
Previous and Unofficial Names Click here for help
somatotropin release-inhibiting factor receptor | SRIF-1
Database Links Click here for help
Specialist databases
GPCRdb ssr2_human (Hs), ssr2_mouse (Mm), ssr2_rat (Rn)
Other databases
Alphafold P30874 (Hs), P30875 (Mm), P30680 (Rn)
ChEMBL Target CHEMBL1804 (Hs), CHEMBL3207 (Mm), CHEMBL2978 (Rn)
DrugBank Target P30874 (Hs)
Ensembl Gene ENSG00000180616 (Hs), ENSMUSG00000047904 (Mm), ENSRNOG00000002793 (Rn)
Entrez Gene 6752 (Hs), 20606 (Mm), 54305 (Rn)
Human Protein Atlas ENSG00000180616 (Hs)
KEGG Gene hsa:6752 (Hs), mmu:20606 (Mm), rno:54305 (Rn)
OMIM 182452 (Hs)
Pharos P30874 (Hs)
RefSeq Nucleotide NM_001050 (Hs), NM_001042606 (Mm), NM_019348 (Rn)
RefSeq Protein NP_001041 (Hs), NP_001036071 (Mm), NP_062221 (Rn)
UniProtKB P30874 (Hs), P30875 (Mm), P30680 (Rn)
Wikipedia SSTR2 (Hs)
Natural/Endogenous Ligands Click here for help
cortistatin-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

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]LTT-SRIF-28 Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.9 – 10.0 pKd 119,133-134
⤷ pKd 9.9 – 10.0 [119,133-134]
[125I]Tyr3 SMS 201-995 Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.9 pKd 134-135
⤷ pKd 9.9 (Kd 1.3x10-10 M) [134-135]
[125I]Tyr10-CST14 Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.4 pKd 133,135
⤷ pKd 9.4 [133,135]
L-054,522 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 11.0 pKi 161
⤷ pKi 11.0 [161]
L-779,976 Small molecule or natural product Hs Full agonist 10.3 pKi 119
⤷ pKi 10.3 [119]
SRIF-14 {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.9 – 10.5 pKi 22,45,99,103,119,133-135,161
⤷ pKi 8.9 – 10.5 [22,45,99,103,119,133-135,161]
BIM 23023 Peptide Click here for species-specific activity table Hs Full agonist 9.4 pKi 99
⤷ pKi 9.4 [99]
BIM 23059 Peptide Click here for species-specific activity table Hs Full agonist 9.4 pKi 99
⤷ pKi 9.4 [99]
L-363,377 Peptide Hs Full agonist 9.3 pKi 119,161
⤷ pKi 9.3 [119,161]
SRIF-28 {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.4 – 10.2 pKi 22,45,99,133-135
⤷ pKi 8.4 – 10.2 [22,45,99,133-135]
octreotide Peptide Approved drug Click here for species-specific activity table Hs Full agonist 8.7 – 9.9 pKi 22,99,133-135,161
⤷ pKi 8.7 – 9.9 [22,99,133-135,161]
lanreotide Peptide Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 8.7 – 9.6 pKi 22,99,133-135
⤷ pKi 8.7 – 9.6 [22,99,133-135]
CST-17 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.8 – 9.3 pKi 45,133,135
⤷ pKi 8.8 – 9.3 [45,133,135]
BIM 23068 Peptide Click here for species-specific activity table Hs Full agonist 8.8 pKi 99
⤷ pKi 8.8 [99]
cortistatin-14 {Sp: Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.4 – 9.0 pKi 133-135
⤷ pKi 8.4 – 9.0 [133-135]
BIM 23056 Peptide Click here for species-specific activity table Hs Full agonist 6.2 – 6.7 pKi 22,133-135
⤷ pKi 6.2 – 6.7 [22,133-135]
pasireotide Peptide Approved drug Rn Agonist 7.8 – 9.1 pEC50 31,67
⤷ pEC50 7.8 – 9.1 (EC50 1.75x10-8 – 8.6x10-10 M) [31,67]
[Ga-DOTA,Tyr3,Thr8]octreotide Peptide Hs Full agonist 9.7 pIC50 8,114
⤷ pIC50 9.7 (IC50 2x10-10 M) [8,114]
[125I][Tyr3,Thr8]octreotide Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.3 pIC50 155
⤷ pIC50 9.3 (IC50 4.7x10-10 M) [155]
[125I]Tyr3 SMS 201-995 Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.9 pIC50 155
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [155]
[111In]DOTA-BOC-ATE Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.8 pIC50 53
⤷ pIC50 8.8 [53]
[111In]DOTA-NOC-ATE Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 pIC50 53
⤷ pIC50 8.7 [53]
[111In]DOTA-NOC Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.5 pIC50 156
⤷ pIC50 8.5 [156]
[111In,90Y]DOTA-NOC Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.4 pIC50 156
⤷ pIC50 8.4 [156]
[111In,90Y]DOTA-TOC Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 7.9 pIC50 156
⤷ pIC50 7.9 [156]
veldoreotide Peptide Click here for species-specific activity table Hs Agonist - - 4
⤷ [4]
View species-specific agonist tables
Agonist Comments
Liu et al (2005) [165] 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 [31,67]. Both ligands exhibit biased agonism: they activate and antagonise distinct signalling pathways [31]. 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 [31].
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[D-Tyr8]CYN 154806 Peptide Click here for species-specific activity table Hs Antagonist 8.1 – 8.9 pKd 97
⤷ pKd 8.1 – 8.9 [97]
BASS antagonist Peptide Hs Antagonist 9.5 pKi 15
⤷ pKi 9.5 (Ki 3x10-10 M) [15]
BIM 23627 Peptide Click here for species-specific activity table Hs Antagonist 8.2 pIC50 147
⤷ pIC50 8.2 [147]
BIM 23454 Peptide Click here for species-specific activity table Hs Antagonist 7.5 pIC50 147
⤷ pIC50 7.5 [147]
DOTA-JR11 Peptide Hs Antagonist - - 30
⤷ [30]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Potassium channel
Calcium channel
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 [19,95].
G-protein-dependent: activation of ERK and PI3K activity in sst2-transfected CHO cells [74] and [58].
Other: Inhibition of L and N voltage gated Ca2++ channels activity [162]. 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 [33,61,82].
Other downstream events reported to be consequential to somatostatin binding include inhibition of the PI3K-mTOR pathway and cap-dependent translation [12,28,144], activation of the protein-tyrosine phosphatases SHP-1, SHP-2 or PTPeta [14,48] and inhibition of eNOS activity [9].
References:  64,68,78,132
Tissue Distribution Click here for help
Other structures: kidney
Species:  Human
Technique:  Immunohistochemistry
References:  50,148
Pancreatic islets: co-localised with glucagon in alpha-cells.
Species:  Human
Technique:  immunocytochemistry.
References:  72
Lymphoid cells.
Species:  Human
Technique:  RT-PCR.
References:  146
Immune system: lymph follicles, granulocytopoietic cells of the bone marrow, alveolar macrophages
Species:  Human
Technique:  Immunohistochemistry
References:  50,148
Pituitary.
Species:  Human
Technique:  RT-PCR.
References:  92
A and B pancreatic islet cells, but not in adjacent acinar cells.
Species:  Human
Technique:  Immunohistochemistry, autoradiography
References:  110
GI tract (gastrointestinal lymphatic and nervous components, but not in gastrointestinal circular and longitudinal smooth muscle).
Species:  Human
Technique:  Immunohistochemistry.
References:  56,111
Lymphoid tissue, plexus.
Species:  Human
Technique:  Immunohistochemistry, autoradiography.
References:  111
Kidney.
Species:  Human
Technique:  Autoradiography.
References:  108
Lymphoid tissue.
Species:  Human
Technique:  Autoradiography, in vivo scintigraphy
References:  109,116
Pancreatic exocrine tissue and pancreatic ductal adenocarcinoma.
Species:  Human
Technique:  Immunohistochemistry, RT-PCR
References:  23,75,145
Peritumoral veins of human tumours.
Species:  Human
Technique:  Radioligand binding.
References:  41
Proliferating endothelium.
Species:  Human
Technique:  Immunocytochemistry.
References:  3
Spleen.
Species:  Human
Technique:  Immunohistochemistry.
References:  49
Macrophages.
Species:  Human
Technique:  RT-PCR.
References:  10
CNS: cerebral cortex, hippocampus, septum, basal forebrain, basal ganglia, amygdala, brainstem, hypothalamus (arcuate nucleus, medial tuberal nucleus, lateroanterior nucleus, ventrocaudal part of the tuber cinereum), cerebellum, spinal cord, retina
Species:  Human
Technique:  Immunohistochemistry
References:  35-36,42,66,120-122,124,126-130
PNS: dorsal root ganglia, enteric ganglion cells and fibers
Species:  Human
Technique:  Immunohistochemistry
References:  111,127,140
Endocrine system: anterior pituitary, endocrine pancreas, adrenal cortex, ovary, testis, neuroendocrine / enterochromaffin-like cells of the GI mucosa
Species:  Human
Technique:  Immunohistochemistry
References:  38,50,65,86,91,100,110,148
Gastrointestinal system: parotid gland, exocrine pancreas
Species:  Human
Technique:  Immunohistochemistry
References:  50,65,148
Cortex, amygdala, claustrum, endopiriform nucleus, arcuate and periventricular nuclei of the hypothalamus, medial habenular nucleus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  20
Parietal cells and ECL cells in stomach, and myenteric neurons.
Species:  Mouse
Technique:  Immunohistochemistry and LacZ knock-in.
References:  6
Expression Datasets Click here for help

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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 Click here for help
Measurement of GH release from rat anterior pituitary.
Species:  Rat
Tissue:  Rat anterior pituitary.
Response measured:  Inhibition of GH release.
References:  104
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:  96
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:  96
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:  29
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:  29
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:  161
Measurement of GH release in in vivo rat studies.
Species:  Rat
Tissue:  In vivo.
Response measured:  Reduction in circulating GH.
References:  161
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:  59
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:  131
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:  40
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:  68
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:  143
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:  132
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:  32
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:  71
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:  76
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
Receptor internalisation.
Species:  Rat
Tissue:  Pituitary
Response measured:  Receptor endocytosis.
References:  60
Receptor internalisation.
Species:  Rat
Tissue:  Pancreatic acinar cells
Response measured:  Receptor endocytosis.
References:  44
Receptor phosphorylation.
Species:  Rat
Tissue:  CHO (Chinese Hamster Ovary) cells
Response measured:  Site specific sst2A phosphorylation.
References:  52,83
Receptor phosphorylation.
Species:  Rat
Tissue:  Pituitary
Response measured:  Receptor phosphorylation.
References:  60
Receptor phosphorylation.
Species:  Human
Tissue:  Neuroendocrine tumours
Response measured:  Receptor phosphorylation.
References:  85
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:  154
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:  115
Physiological Functions Click here for help
Inhibition of GH release (synergistic with sst5).
Species:  Human
Tissue:  Primary fetal pituitary cell culture.
References:  105
Inhibition of gastric acid secretion.
Species:  Mouse
Tissue:  Stomach.
References:  89,101
Inhibition of histamine release leading to inhibition of gastric acid release.
Species:  Mouse
Tissue:  Stomach.
References:  70
Inhibition of glucagon release.
Species:  Mouse
Tissue:  Pancreas.
References:  141
Control of dopamine and glutamate release in the striatum.
Species:  Mouse
Tissue:  Striatum.
References:  7
Stimulation of ductile bile absorption and inhibition of ductile bile secretion.
Species:  Mouse
Tissue:  Cholangiocytes.
References:  55
Inhibition of peristalsis in the jejunum.
Species:  Mouse
Tissue:  Jejunum.
References:  1
Inhibition of peristalsis in the jejunum.
Species:  Rat
Tissue:  Jejunum.
References:  1
Lymphocyte activation, development and tumorgenesis.
Species:  Human
Tissue:  Lymphatic cells.
References:  146
Decrease in AMPA/Kainate receptor-mediated responses to glutamate.
Species:  Mouse
Tissue:  Hypothalamic neurones grown in primary cell culture.
References:  76
Inhibition of GH release (with sst3).
Species:  Rat
Tissue:  Hepatocytes (liver cells).
References:  94
Inhibition of cell proliferation in vivo.
Species:  Rat
Tissue:  Glioma.
References:  13
Inhibition of glucagon release.
Species:  Rat
Tissue:  Batch incubations of isolated rat islets, perifused isolated rat islets, and isolated perfused rat pancreas.
References:  27
Positive regulation of neuronal migration during brain development, inhibition of keratinocyte migration and delay in epidermal wound healing
Species:  Human
Tissue:  Brain, epidermis.
References:  79,153
Inhibition of insulin and glucagon secretion.
Species:  Human
Tissue:  Isolated human pancreatic islet cells.
References:  136
Positive regulation of food intake, grooming behaviour and rectal temperature.
Species:  Rat
Tissue:  Brain.
References:  139
Anxiolytic effects in both the amygdala and the septum.
Species:  Rat
Tissue:  Brain.
References:  163
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:  2,51,57,73,77,118,142,157
Modulation of in vivo gamma oscillation and odor discrimination.
Species:  Mouse
Tissue:  Olfactory bulb.
References:  80
Physiological Consequences of Altering Gene Expression Click here for help
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:  25
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:  7
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:  141
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:  101
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:  1
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:  164
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:  21
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:  152
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:  93
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:  89
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:  152
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:  137
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:  37
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:  2
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:  17,24,39,57,75,118,150
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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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 Click here for help
Disease:  Endocrine tumors
Role:  Indium-111-pentetreotide scintigraphy and somatostatin receptor expression are new prognosis factors for malignant well-differentiated endocrine tumours.
References:  11
Disease:  Gastrointestinal neuroendocrine tumor
Disease Ontology: DOID:4148
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 neuroendocrine tumors (NETs).
References:  117
Disease:  Insulinoma
Disease Ontology: DOID:3892
Orphanet: ORPHA97279
Role:  Octreotide efficacy on hypoglycemia in insulinoma patients correlates with positive anti-sst2A immunostaining.
References:  151
Gene Expression and Pathophysiology Click here for help
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:  18
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:  102
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Mouse
Description:  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).
References:  149
Type:  Single nucleotide polymorphism
Species:  Human
Description:  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).
SNP accession:  rs1466113
References:  138
Type:  Splice variant
Species:  Human
Description:  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.
References:  98
Type:  Splice variant
Species:  Rat
Description:  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.
References:  123
General Comments
The sst2 receptor can be targeted by somatostatin analogues to inhibit hormone secretion for pituitary tumors and GEP-NET [34]. The receptor can also be targeted for nuclear imaging and radionuclide treatment [87].

References

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