Somatostatin receptor 2: Difference between revisions

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'''Somatostatin receptor type 2''' is a [[protein]] that in humans is encoded by the ''SSTR2'' [[gene]].<ref name="pmid8449518">{{cite journal | vauthors = Yamada Y, Stoffel M, Espinosa R, Xiang KS, Seino M, Seino S, Le Beau MM, Bell GI | title = Human somatostatin receptor genes: localization to human chromosomes 14, 17, and 22 and identification of simple tandem repeat polymorphisms | journal = Genomics | volume = 15 | issue = 2 | pages = 449–52 | date = February 1993 | pmid = 8449518 | pmc = | doi = 10.1006/geno.1993.1088 }}</ref>
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The SSTR2 gene is located on chromosome 17 on the long arm in position 25.1 in humans.<ref>{{Cite web |url= https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:11331 |title=SSTR2 Symbol Report | work = HUGO Gene Nomenclature Committee }}</ref> It is also found in most other vertebrates.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/?Term=ortholog_gene_6752%5Bgroup%5D|title=ortholog_gene_6752[group] - Gene | work = NCBI }}</ref>
{{GNF_Protein_box
| image =
| image_source = 
| PDB =
| Name = Somatostatin receptor 2
| HGNCid = 11331
| Symbol = SSTR2
| AltSymbols =;
| OMIM = 182452
| ECnumber = 
| Homologene = 37427
| MGIid = 98328
| GeneAtlas_image1 = PBB_GE_SSTR2_214597_at_tn.png
| GeneAtlas_image2 = PBB_GE_SSTR2_217455_s_at_tn.png
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004994 |text = somatostatin receptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0030165 |text = PDZ domain binding}}
| Component = {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007187 |text = G-protein signaling, coupled to cyclic nucleotide second messenger}} {{GNF_GO|id=GO:0007193 |text = G-protein signaling, adenylate cyclase inhibiting pathway}} {{GNF_GO|id=GO:0007218 |text = neuropeptide signaling pathway}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0007584 |text = response to nutrient}} {{GNF_GO|id=GO:0007586 |text = digestion}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6752
    | Hs_Ensembl = ENSG00000180616
    | Hs_RefseqProtein = NP_001041
    | Hs_RefseqmRNA = NM_001050
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 68672755
    | Hs_GenLoc_end = 68679655
    | Hs_Uniprot = P30874
    | Mm_EntrezGene = 20606
    | Mm_Ensembl = ENSMUSG00000047904
    | Mm_RefseqmRNA = XM_990740
    | Mm_RefseqProtein = XP_995834
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 113440347
    | Mm_GenLoc_end = 113441726
    | Mm_Uniprot = P30875
  }}
}}
'''Somatostatin receptor 2''', also known as '''SSTR2''', is a human [[gene]].


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The somatostatin receptor 2 (SSTR2), which belongs to the [[G-protein coupled receptor]] family, is a protein which is most highly expressed in the [[pancreas]] (both alpha- and beta-cells), but also in other tissues such as the [[cerebrum]] and kidney and in lower amount in the [[jejunum]], [[Large intestine|colon]] and liver.<ref name = "UniProt_ P30874" /><ref>{{cite web | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=SSTR2 |title=SSTR2 Gene | work = GeneCards Human Gene Database Gene }}</ref><ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=6752 |title=SSTR2 somatostatin receptor 2 [Homo sapiens (human)] - Gene  | work = NCBI }}</ref> In the pancreas, after binding to [[somatostatin]], it inhibits the secretion of pancreatic enzymes.<ref name = "UniProt_ P30874" /> During development, it stimulates [[neuronal migration]] and [[growth cone|axon outgrowth]].<ref name = "UniProt_ P30874">{{UniProt Full|P30874|SSTR2 - Somatostatin receptor type 2 - Homo sapiens (Human)}}</ref>
{{PBB_Summary
| section_title =
| summary_text = Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biologic effects of somatostatin are probably mediated by a family of G protein-coupled receptors that are expressed in a tissue-specific manner. SSTR2 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in cerebrum and kidney.<ref name="entrez">{{cite web | title = Entrez Gene: SSTR2 somatostatin receptor 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6752| accessdate = }}</ref>
}}


==See also==
The somatostatin receptor 2 is expressed in most tumors.<ref>{{cite journal | vauthors = Reubi JC, Waser B, Schaer JC, Laissue JA | title = Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands | journal = European Journal of Nuclear Medicine | volume = 28 | issue = 7 | pages = 836–46 | date = July 2001 | pmid = 11504080 | doi = 10.1007/s002590100541 }}</ref> Patients with neuroendocrine tumors that over-express the somatostatin receptor 2 have an improved prognosis.<ref>{{cite journal | vauthors = Wang Y, Wang W, Jin K, Fang C, Lin Y, Xue L, Feng S, Zhou Z, Shao C, Chen M, Yu X, Chen J | title = Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors | journal = Oncology Letters | volume = 13 | issue = 3 | pages = 1165–1174 | date = March 2017 | pmid = 28454229 | pmc = 5403486 | doi = 10.3892/ol.2017.5591 }}</ref>  The over expression of SSTR2 is tumors can be exploited to selectively deliver radio-peptides to tumors to either detect or destroy them.<ref>{{Cite web|url=https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/113597|title=SSTR2 - Clinical: Somatostatin Receptor 2 (SSTR2), Immunostain, Technical Component Only|website=www.mayomedicallaboratories.com |access-date=2018-11-10}}</ref> Somatostatin receptor 2 also has the ability to stimulate [[apoptosis]] in many cells including cancer cells.<ref>{{cite journal | vauthors = Teijeiro R, Rios R, Costoya JA, Castro R, Bello JL, Devesa J, Arce VM | title = Activation of human somatostatin receptor 2 promotes apoptosis through a mechanism that is independent from induction of p53 | language = english | journal = Cellular Physiology and Biochemistry | volume = 12 | issue = 1 | pages = 31–8 | date = 2002 | pmid = 11914546 | doi = 10.1159/000047824 }}</ref> The somatostatin receptor 2 is also being looked at as a possible target in cancer treatment for its ability to inhibit tumor growth.<ref>{{cite journal | vauthors = Callison JC, Walker RC, Massion PP | title = Somatostatin Receptors in Lung Cancer: From Function to Molecular Imaging and Therapeutics | journal = Journal of Lung Cancer | volume = 10 | issue = 2 | pages = 69–76 | date = 2011 | pmid = 25663834 | pmc = 4319675 | doi = 10.6058/jlc.2011.10.2.69 }}</ref>
* [[Somatostatin receptor]]


==References==
== Function ==
{{reflist|2}}


==Further reading==
The gene for somatostatin receptor 2, SSTR2 for short, is responsible for making a receptor for the signalling peptide, somatostatin (SST). Production occurs in the central nervous system, especially the hypothalamus, as well as the digestive system, and pancreas.<ref name = "Kailey_2012">{{cite journal | vauthors = Kailey B, van de Bunt M, Cheley S, Johnson PR, MacDonald PE, Gloyn AL, Rorsman P, Braun M | title = SSTR2 is the functionally dominant somatostatin receptor in human pancreatic β- and α-cells | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 303 | issue = 9 | pages = E1107-16 | date = November 2012 | pmid = 22932785 | pmc = 3492856 | doi = 10.1152/ajpendo.00207.2012 }}</ref> SSTR2 is a receptor for somatostatin-14 and -28 respectively. The numbers 14 and 28 represent the amount of amino acids in each protein sequence.<ref name = "Kailey_2012" /> All somatostatin receptors including SSTR2 may have different specific functions, but all fall under the same receptor super family, the G-protein binding family and all of which are a major inhibitor for other hormones.<ref>{{Cite web|url=http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/somatostatin.html|title=Somatastatin|website=www.vivo.colostate.edu|language=en|access-date=2018-11-07}}</ref> For all somatostatin inhibitors, somatostatin-14 and -28 work by binding to the receptor with the help of a G-protein. This inhibits adenylyl cyclase and calcium channels. These proteins are released in various parts of the human body and vary in the amount emitted from each organ system. In secretory cells this protein is in a greater volume compared to amount released from activated immune and inflammatory cells. These proteins have a tendency of being emitted in response to items such as: ions, nutrients, neuropeptides, neurotransmitters, hormones, growth factors, and cytokines.<ref name = "Patel_1999">{{cite journal | vauthors = Patel YC | title = Somatostatin and its receptor family | journal = Frontiers in Neuroendocrinology | volume = 20 | issue = 3 | pages = 157–98 | date = July 1999 | pmid = 10433861 | doi = 10.1006/frne.1999.0183 }}</ref>
 
In general, somatostatin can put a cell in cycle arrest using the phosphotyrosine phosphatase dependent regulation of mitrogen-activated protein kinase, this process can lead to a halt in the cell cycle or apoptosis of the cell and is used as a tumor suppressor in the genome. This hormone is also known to perform agonist-dependent endocytosis, which allows a cell to take in receptors, ions, and other molecules.<ref name = "Patel_1999" />
 
Because this protein is found in multiple organs, it has a different specific role in each organ or organ system. A major function of the protein made by the gene SSTR2 is pancreatic interaction with the alpha and beta cells. In the delta cells of the pancreas, this hormone inhibits the secretion of both glucagon and insulin in the alpha and beta cells when stimulated by basic nutrients like sugars, proteins, and fats.<ref>{{cite journal | vauthors = Bhandari S, Watson N, Long E, Sharpe S, Zhong W, Xu SZ, Atkin SL | title = Expression of somatostatin and somatostatin receptor subtypes 1-5 in human normal and diseased kidney | journal = The Journal of Histochemistry and Cytochemistry | volume = 56 | issue = 8 | pages = 733–43 | date = August 2008 | pmid = 18443363 | pmc = 2443611 | doi = 10.1369/jhc.2008.950998 }}</ref> In fact, this protein, is the dominant one out of all of the somatostatins in the pancreas. In the stomach, it reduces activity of the digestive tract by inhibiting secretion of gastric acid, pepsin, bile, and colonic acid when in the presence of luminal nutrients; all of these secretions are needed for proper digestion. It also represses motor activity in the gut  by blocking segmentation of the intestines, gallbladder contraction, and emptying of the bowels.This inhibition by somatostatin allows the body to uptake the maximum amount of nutrients in the digestive system.<ref>{{cite book |last=Carroll |first=Robert G. | name-list-format = vanc |title=Endocrine System |date=2007 |work=Elsevier's Integrated Physiology |pages=157–176 |publisher=Elsevier |doi=10.1016/b978-0-323-04318-2.50019-4 |isbn=9780323043182 }}</ref> Along with the gut and pancreas, SSTR2 also inhibits secretion of neurotransmitters in the central and peripheral nervous system. These hormones include dopamine, norpinephrine, thyrotropin-releasing hormone, and corticotropin-releasing hormone. Many of these hormones help the body maintain homeostasis or react properly to a stimulus such as something pleasurable or a stress in the environment. Because of which, the receptors for somatostatin type 2 impact the body's locomotor, sensory, autonomic, and cognitive functions.
 
== Interactions ==
 
Somatostatin receptor 2 has been shown to [[Protein-protein interaction|interact]] with [[SHANK2]].<ref name=pmid10551867>{{cite journal | vauthors = Zitzer H, Hönck HH, Bächner D, Richter D, Kreienkamp HJ | title = Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain | journal = The Journal of Biological Chemistry | volume = 274 | issue = 46 | pages = 32997–3001 | date = November 1999 | pmid = 10551867 | doi = 10.1074/jbc.274.46.32997 }}</ref>
 
== Clinical significance ==
The somatostatin hormone itself can negatively affect the uptake of hormones in the body and may play a role in some hormonal conditions. Somatostatin 2 receptors have been found in concentration on the surface of tumor cells, particularly those associated with the neuroendocrine system where the overexpression of somatostatin can lead to many complications<ref>{{Cite web|url=http://www.med.harvard.edu/jpnm/tf94_95/nov1/writeupnov1.html|title=Joint Program in Nuclear Medicine|website=www.med.harvard.edu|access-date=2018-11-16}}</ref><ref name = "Childs_2016">{{cite journal | vauthors = Childs A, Vesely C, Ensell L, Lowe H, Luong TV, Caplin ME, Toumpanakis C, Thirlwell C, Hartley JA, Meyer T | title = Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours | journal = British Journal of Cancer | volume = 115 | issue = 12 | pages = 1540–1547 | date = December 2016 | pmid = 27875519 | pmc = 5155369 | doi = 10.1038/bjc.2016.377 }}</ref> Due to this, these receptors are considered a prospective aid for the detection of tumors, especially in patients who present with conditions like hypothyroidism and Cushing’s syndrome.<ref name=":3">{{cite journal | vauthors = Yu B, Zhang Z, Song H, Chi Y, Shi C, Xu M | title = Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma) | journal = Medical Science Monitor | volume = 23 | pages = 1947–1955 | date = April 2017 | pmid = 28434012 | pmc = 5411020 | doi = 10.12659/MSM.903377 }}</ref><ref name="pmid9825485">{{cite journal | vauthors = Kennedy JW, Dluhy RG | title = The biology and clinical relevance of somatostatin receptor scintigraphy in adrenal tumor management | journal = The Yale Journal of Biology and Medicine | volume = 70 | issue = 5-6 | pages = 565–75 | date = 1997 | pmid = 9825485 | pmc = 2589262 | doi = | url = }}</ref> A synthetic version of the somatostatin hormone, octreotide, has been successfully used in combination with radio-peptide tracers to locate adrenal gland tumors through scintigraphic imaging.<ref name=":4">{{Cite journal | vauthors = Hofmann M, Gazdhar A, Weitzel T, Schmid R, Krause T | title = PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy. | journal = Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | date = December 2006 | volume = 569 | issue = 2 | pages = 509–11 | doi=10.1016/j.nima.2006.08.161 }}</ref> A similar method may be utilized to carry and more accurately administer radioactive treatments to tumors.<ref name=":4" /> Octreotide and other analogs are preferred for this use due to their possessing of an extended half life compared to the naturally-occurring hormone allowing for more flexibility when used for such treatments.<ref name="pmid9825485"/>
 
The association of somatostatin 2 receptors on tumors has also lead to the suggestion of possible alternatives to current tumor treatment methods. The binding of synthetic somatostatin hormones such as octreotide to receptors has been seen to reduce the production of hormones and is now being considered for use in the treatment of some pituitary tumors. One group suggests that the treatment method would be particularly effective against thyrotropin-secreting pituitary adenomas (TSHomas), though further inquiries and clinical trials are needed.<ref name=":3" />
 
SSTR2 is also being investigated for its potential use as a reporter gene for the visualization of regional gene expression. One study tested this by comparing the PET/CT and light imaging results of laboratory rats’ musculature obtained through the use of a human somatostatin receptor 2 vector and a control luciferase vector.<ref name=":4" /> The study suggests that somatostatin receptor genes could be an effective substitute for the current viral-based vectors since the sstr genes elicits less of an immune response and has overall been well-tolerated by the trial patients’ bodies. This form of treatment may be especially useful for the study of gene expression in larger mammals whose larger body mass may obstruct clear visualization of deep tissue areas.<ref name=":4" /> The use of sstr2 and sstr5 as biomarkers to track the progress of and treat neuroendocrine tumors displaying circulating tumor cells is also being investigated due to these cells’ somatostatin receptor gene expressivity.<ref name = "Childs_2016" />
 
== Therapeutic targeting ==
 
Most [[pituitary adenomas]] express [[SSTR2]], but other [[somatostatin receptors]] are also found.<ref name="pmid7714115">{{cite journal | vauthors = Miller GM, Alexander JM, Bikkal HA, Katznelson L, Zervas NT, Klibanski A | title = Somatostatin receptor subtype gene expression in pituitary adenomas | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 80 | issue = 4 | pages = 1386–92 | date = April 1995 | pmid = 7714115 | doi = 10.1210/jcem.80.4.7714115 }}</ref> [[Somatostatin]] analogs (i.e. [[Octreotide]], [[Lanreotide]] ) are used to stimulate these receptors, and thus to inhibit further tumor proliferation.<ref name="pmid17413185">{{cite journal | vauthors = Zatelli MC, Ambrosio MR, Bondanelli M, Uberti EC | title = Control of pituitary adenoma cell proliferation by somatostatin analogs, dopamine agonists and novel chimeric compounds | journal = European Journal of Endocrinology | volume = 156 Suppl 1 | issue =  | pages = S29-35 | date = April 2007 | pmid = 17413185 | doi = 10.1530/eje.1.02352 }}</ref>
 
== Discovery ==
There is a group of somatostatin receptors called the somatostatin receptor family. All of the members of the somatostatin receptor family are proteins that sit on the surface of the cell membrane and are responsible for the communication between cells.<ref>{{Cite web|url=https://www.ibiblio.org/virtualcell/textbook/chapter3/cmf3.htm|title=The Virtual Cell Textbook - Cell Biology|website=www.ibiblio.org|access-date=2018-11-07}}</ref> In 1972,<ref name=":1">{{cite journal | vauthors = Møller LN, Stidsen CE, Hartmann B, Holst JJ | title = Somatostatin receptors | journal = Biochimica et Biophysica Acta | volume = 1616 | issue = 1 | pages = 1–84 | date = September 2003 | pmid = 14507421 | doi = 10.1016/S0005-2736(03)00235-9 }}</ref> scientists were on the trek to discover more information on the hypothalamus and its "release factors."<ref name=":1" /> Studies showed patterns of inhibitory activity of the hypothalamus release factors which led scientists in the direction to discover somatostatin, known as the somatropin release-inhibiting factor, or SRIF. We now know that the SRIF is located at 3q28 (long arm of the third chromosome at the twenty-eighth position) in humans.<ref name=":1" /> Peering into location 3q28, the majority of proteins code for the pancreas, ovaries, and prostate along with other components of the endocrine system and nervous system,<ref>{{Cite web |url=http://atlasgeneticsoncology.org/Bands/3q28.html |title=Chromosome 3 |website=atlasgeneticsoncology.org|access-date=2018-11-09}}</ref> so it can be drawn that the receptor family has great influence among these systems. The family was first discovered in a segment of a rat's pituitary gland known as the tumor cell line.<ref name = "GTP" >{{cite web |url=http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=61|title= Somatostatin receptors | work = IUPHAR/BPS Guide to Pharmacology }}</ref> A cell line is grown as a culture under controlled conditions, so the first discovery was found by culturing these cells in controlled conditions and in an environment outside of its norm. There, researchers found that the tumor cell line expresses a cell dividing inhibitor known as the transforming growth factor beta (TGF-beta) <ref>{{cite journal | vauthors = Yamashita H, Okadome T, Franzén P, ten Dijke P, Heldin CH, Miyazono K | title = A rat pituitary tumor cell line (GH3) expresses type I and type II receptors and other cell surface binding protein(s) for transforming growth factor-beta | journal = The Journal of Biological Chemistry | volume = 270 | issue = 2 | pages = 770–4 | date = January 1995 | pmid = 7822309 }}</ref> and also acts as an inhibitor to the milk producing hormone in female mammals, prolactin, and growth hormones. Researchers studied the activity of the receptors by conducting an assay with Ligand binding studies,<ref name = "GTP" /> which basically means they were conducting studies to see how prevalent the binding of the receptors occurred.<ref>{{Cite news|url=https://www.medicinenet.com/script/main/art.asp?articlekey=8412|title=Definition of Assay|work=MedicineNet|access-date=2018-11-09|language=en}}</ref><ref name="GTP" /> Differences in how prevalently they receptors bonded revealed the existence of multiple receptors.<ref name="GTP" /> Based on the ligand binding affinity and the receptors' signaling mechanisms, the receptor family was divided into 2 different groups, and within those groups, 5 subgroups. The group with a high affinity binding were classified under the SRIF1 group with sst2, sst3, and sst5 in the subgroup, while the receptors with low affinity binding were classified under the SRIF2 group with sst1 and sst4 in the subgroup. Manipulations with the somatostatin receptors are used for many therapies in both the endocrine and nervous system, and now that we know the groups and subgroups of the receptor family, therapy treatment is much more efficient and effective. For example, as you continue reading the article, you will notice the importance and advancements of oncology and tumor treatments, as well as other ways the somatostatin receptors are working and advancing the world of medicine.<ref>{{Cite web| url=http://www.yourhormones.info/hormones/prolactin/ |title=Prolactin | work = You and Your Hormones | publisher = Society for Endocrinology |access-date=2018-11-07}}</ref>
 
The somatostatin receptor 2 is found on the chromosome 17.<ref name=":2">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/6752|title=SSTR2 somatostatin receptor 2 [Homo sapiens (human)] | work = NCBI }}</ref> Information was gathered and determined from a sample of individuals, and conclusions were drawn upon location and other information regarding the SSRT2 protein.<ref name=":2" />
{| class="wikitable"
|Gene:
|SSTR2
|-
|Title:
|somatostatin receptor 2
|-
|Location:
|73,165,021..73,171,955
|-
|Length:
|6,935 nt
|-
|[''Positional Info'']
| colspan="0" |
|-
|NC_000017.11 position:
|73,168,608
|-
|Gene position:
|3,588
|}
 
== Isoforms ==
Like other proteins, the somatostatin receptor 2 also has variants. Somatostatin receptor 2 exists in two [[Protein isoform|isoforms]] that are different in carboxy-terimini compositions and size. [[Alternative splicing]] of the somatostatin receptor 2 mRNA resulted in two variants, somatostatin receptor 2a (SSTR2A) and somatostatin receptor 2b (SSTR2B). In a rodent, somatostatin receptor 2a is longer compared to the shorter somatostatin receptor 2b. Isoform a and isoform b sequences are different, beginning at the C-terminal regulatory domains.<ref name=":0">{{cite journal | vauthors = Vanetti M, Ziólkowska B, Wang X, Horn G, Höllt V | title = mRNA distribution of two isoforms of somatostatin receptor 2 (mSSTR2A and mSSTR2B) in mouse brain | journal = Brain Research. Molecular Brain Research | volume = 27 | issue = 1 | pages = 45–50 | date = November 1994 | pmid = 7877453 | doi = 10.1016/0169-328X(94)90182-1 }}</ref> Studies have shown that carboxy-terminal splicing has occurred in many other transmembrane receptors, along with prostaglandin E receptor (EP3).<ref name = "Schulz_1998">{{cite journal | vauthors = Schulz S, Schmidt H, Händel M, Schreff M, Höllt V | title = Differential distribution of alternatively spliced somatostatin receptor 2 isoforms (sst2A and sst2B) in rat spinal cord | journal = Neuroscience Letters | volume = 257 | issue = 1 | pages = 37–40 | date = November 1998 | pmid = 9857960 | doi = 10.1016/s0304-3940(98)00803-9 }}</ref> These variants, SST2A receptor and SST2B receptor are seen in some brain and spinal cord areas in a rodent.<ref name="pmid8386508">{{cite journal | vauthors = Patel YC, Greenwood M, Kent G, Panetta R, Srikant CB | title = Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation | journal = Biochemical and Biophysical Research Communications | volume = 192 | issue = 1 | pages = 288–94 | date = April 1993 | pmid = 8386508 | doi = 10.1006/bbrc.1993.1412 }}</ref> Somatostatin receptor 2a has a shorter transcript, but is longer then somatostatin receptor 2b and has a unique C- terminus compared to Somatostatin Receptor 2b.<ref name = "Schulz_1998" /> SSTRB receptor has approximately 300 nucleotides between carboxyl terminus and transmembrane segments fewer then the original Somatostatin receptor 2. SST2A receptor is made up of 369 amino acids and 346 amino acids make up the SST2B receptor.<ref>{{Cite journal|date=2003-09-22|title=Somatostatin receptors |journal=Biochimica et Biophysica Acta (BBA) - Biomembranes |volume=1616|issue=1|pages=1–84|doi=10.1016/S0005-2736(03)00235-9|issn=0005-2736}}</ref> Somatostatin receptor 2a and somatostatin receptor 2b were found in the medulla oblongata, mesencephalon, testis, cortex, hypothalamus, hippocampus and pituitary of a rodent, using reverse transcription polymerase chain reaction (RT-PCR).<ref name=":0" /> Somatostatin receptor 2a is highly evident in the cortex, but the somatostatin receptor 2b is not seen as much. The medeulla oblongata shows equal amounts of the two variants being expressed. The Somatostatin receptor 2a was found mostly in far down layers of the cerebral cortex, in the human brain. This variant of the Somatostatin receptor was found with the use of immunohistochemistry.<ref name="pmid11088000">{{cite journal | vauthors = Cole SL, Schindler M | title = Characterisation of somatostatin sst2 receptor splice variants | journal = Journal of Physiology, Paris | volume = 94 | issue = 3-4 | pages = 217–37 | date = 2000 | pmid = 11088000 | doi = 10.1016/S0928-4257(00)00207-2 }}</ref> The difference in ratios of the isoforms imply a tissue-specific control of transcription. Somatostatin receptor 2b is not shown expressed without somatostatin receptor 2a in the brain.<ref name=":0" />
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Yamada Y, Post SR, Wang K, Tager HS, Bell GI, Seino S | title = Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 1 | pages = 251–5 | date = January 1992 | pmid = 1346068 | pmc = 48214 | doi = 10.1073/pnas.89.1.251 }}
| citations =
* {{cite journal | vauthors = Reubi JC, Waser B, Schaer JC, Markwalder R | title = Somatostatin receptors in human prostate and prostate cancer | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 80 | issue = 9 | pages = 2806–14 | date = September 1995 | pmid = 7673428 | doi = 10.1210/jc.80.9.2806 }}
*{{cite journal | author=Yamada Y, Post SR, Wang K, ''et al.'' |title=Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 1 |pages= 251-5 |year= 1992 |pmid= 1346068 |doi= }}
* {{cite journal | vauthors = Kagimoto S, Yamada Y, Kubota A, Someya Y, Ihara Y, Yasuda K, Kozasa T, Imura H, Seino S, Seino Y | title = Human somatostatin receptor, SSTR2, is coupled to adenylyl cyclase in the presence of Gi alpha 1 protein | journal = Biochemical and Biophysical Research Communications | volume = 202 | issue = 2 | pages = 1188–95 | date = July 1994 | pmid = 7914078 | doi = 10.1006/bbrc.1994.2054 }}
*{{cite journal | author=Reubi JC, Waser B, Schaer JC, Markwalder R |title=Somatostatin receptors in human prostate and prostate cancer. |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue= 9 |pages= 2806-14 |year= 1995 |pmid= 7673428 |doi= }}
* {{cite journal | vauthors = Fujita T, Yamaji Y, Sato M, Murao K, Takahara J | title = Gene expression of somatostatin receptor subtypes, SSTR1 and SSTR2, in human lung cancer cell lines | journal = Life Sciences | volume = 55 | issue = 23 | pages = 1797–806 | year = 1994 | pmid = 7968260 | doi = 10.1016/0024-3205(94)90090-6 }}
*{{cite journal | author=Kagimoto S, Yamada Y, Kubota A, ''et al.'' |title=Human somatostatin receptor, SSTR2, is coupled to adenylyl cyclase in the presence of Gi alpha 1 protein. |journal=Biochem. Biophys. Res. Commun. |volume=202 |issue= 2 |pages= 1188-95 |year= 1994 |pmid= 7914078 |doi= 10.1006/bbrc.1994.2054 }}
* {{cite journal | vauthors = Patel YC, Greenwood M, Kent G, Panetta R, Srikant CB | title = Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation | journal = Biochemical and Biophysical Research Communications | volume = 192 | issue = 1 | pages = 288–94 | date = April 1993 | pmid = 8386508 | doi = 10.1006/bbrc.1993.1412 }}
*{{cite journal | author=Fujita T, Yamaji Y, Sato M, ''et al.'' |title=Gene expression of somatostatin receptor subtypes, SSTR1 and SSTR2, in human lung cancer cell lines. |journal=Life Sci. |volume=55 |issue= 23 |pages= 1797-806 |year= 1994 |pmid= 7968260 |doi= }}
* {{cite journal | vauthors = Fukusumi S, Kitada C, Takekawa S, Kizawa H, Sakamoto J, Miyamoto M, Hinuma S, Kitano K, Fujino M | title = Identification and characterization of a novel human cortistatin-like peptide | journal = Biochemical and Biophysical Research Communications | volume = 232 | issue = 1 | pages = 157–63 | date = March 1997 | pmid = 9125122 | doi = 10.1006/bbrc.1997.6252 }}
*{{cite journal | author=Patel YC, Greenwood M, Kent G, ''et al.'' |title=Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. |journal=Biochem. Biophys. Res. Commun. |volume=192 |issue= 1 |pages= 288-94 |year= 1993 |pmid= 8386508 |doi= 10.1006/bbrc.1993.1412 }}
* {{cite journal | vauthors = Jaïs P, Terris B, Ruszniewski P, LeRomancer M, Reyl-Desmars F, Vissuzaine C, Cadiot G, Mignon M, Lewin MJ | title = Somatostatin receptor subtype gene expression in human endocrine gastroentero-pancreatic tumours | journal = European Journal of Clinical Investigation | volume = 27 | issue = 8 | pages = 639–44 | date = August 1997 | pmid = 9279525 | doi = 10.1046/j.1365-2362.1997.1740719.x }}
*{{cite journal | author=Yamada Y, Stoffel M, Espinosa R, ''et al.'' |title=Human somatostatin receptor genes: localization to human chromosomes 14, 17, and 22 and identification of simple tandem repeat polymorphisms. |journal=Genomics |volume=15 |issue= 2 |pages= 449-52 |year= 1993 |pmid= 8449518 |doi= 10.1006/geno.1993.1088 }}
* {{cite journal | vauthors = Lopez F, Estève JP, Buscail L, Delesque N, Saint-Laurent N, Théveniau M, Nahmias C, Vaysse N, Susini C | title = The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling | journal = The Journal of Biological Chemistry | volume = 272 | issue = 39 | pages = 24448–54 | date = September 1997 | pmid = 9305905 | doi = 10.1074/jbc.272.39.24448 }}
*{{cite journal | author=Fukusumi S, Kitada C, Takekawa S, ''et al.'' |title=Identification and characterization of a novel human cortistatin-like peptide. |journal=Biochem. Biophys. Res. Commun. |volume=232 |issue= 1 |pages= 157-63 |year= 1997 |pmid= 9125122 |doi= 10.1006/bbrc.1997.6252 }}
* {{cite journal | vauthors = Tsutsumi A, Takano H, Ichikawa K, Kobayashi S, Koike T | title = Expression of somatostatin receptor subtype 2 mRNA in human lymphoid cells | journal = Cellular Immunology | volume = 181 | issue = 1 | pages = 44–9 | date = October 1997 | pmid = 9344495 | doi = 10.1006/cimm.1997.1193 }}
*{{cite journal | author=Jaïs P, Terris B, Ruszniewski P, ''et al.'' |title=Somatostatin receptor subtype gene expression in human endocrine gastroentero-pancreatic tumours. |journal=Eur. J. Clin. Invest. |volume=27 |issue= 8 |pages= 639-44 |year= 1997 |pmid= 9279525 |doi= }}
* {{cite journal | vauthors = Sharma K, Patel YC, Srikant CB | title = C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest | journal = Molecular Endocrinology | volume = 13 | issue = 1 | pages = 82–90 | date = January 1999 | pmid = 9892014 | doi = 10.1210/me.13.1.82 }}
*{{cite journal | author=Lopez F, Estève JP, Buscail L, ''et al.'' |title=The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. |journal=J. Biol. Chem. |volume=272 |issue= 39 |pages= 24448-54 |year= 1997 |pmid= 9305905 |doi= }}
* {{cite journal | vauthors = Kumar U, Sasi R, Suresh S, Patel A, Thangaraju M, Metrakos P, Patel SC, Patel YC | title = Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis | journal = Diabetes | volume = 48 | issue = 1 | pages = 77–85 | date = January 1999 | pmid = 9892225 | doi = 10.2337/diabetes.48.1.77 }}
*{{cite journal | author=Tsutsumi A, Takano H, Ichikawa K, ''et al.'' |title=Expression of somatostatin receptor subtype 2 mRNA in human lymphoid cells. |journal=Cell. Immunol. |volume=181 |issue= 1 |pages= 44-9 |year= 1997 |pmid= 9344495 |doi= 10.1006/cimm.1997.1193 }}
* {{cite journal | vauthors = Zitzer H, Richter D, Kreienkamp HJ | title = Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin-binding protein 1 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 26 | pages = 18153–6 | date = June 1999 | pmid = 10373412 | doi = 10.1074/jbc.274.26.18153 }}
*{{cite journal | author=Sharma K, Patel YC, Srikant CB |title=C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest. |journal=Mol. Endocrinol. |volume=13 |issue= 1 |pages= 82-90 |year= 1999 |pmid= 9892014 |doi= }}
* {{cite journal | vauthors = Petersenn S, Rasch AC, Presch S, Beil FU, Schulte HM | title = Genomic structure and transcriptional regulation of the human somatostatin receptor type 2 | journal = Molecular and Cellular Endocrinology | volume = 157 | issue = 1-2 | pages = 75–85 | date = November 1999 | pmid = 10619399 | doi = 10.1016/S0303-7207(99)00161-6 }}
*{{cite journal | author=Kumar U, Sasi R, Suresh S, ''et al.'' |title=Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. |journal=Diabetes |volume=48 |issue= 1 |pages= 77-85 |year= 1999 |pmid= 9892225 |doi= }}
* {{cite journal | vauthors = Kreienkamp HJ, Zitzer H, Richter D | title = Identification of proteins interacting with the rat somatostatin receptor subtype 2 | journal = Journal of Physiology, Paris | volume = 94 | issue = 3-4 | pages = 193–8 | year = 2001 | pmid = 11087996 | doi = 10.1016/S0928-4257(00)00204-7 }}
*{{cite journal | author=Zitzer H, Richter D, Kreienkamp HJ |title=Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin-binding protein 1. |journal=J. Biol. Chem. |volume=274 |issue= 26 |pages= 18153-6 |year= 1999 |pmid= 10373412 |doi= }}
* {{cite journal | vauthors = Ho MK, Yung LY, Chan JS, Chan JH, Wong CS, Wong YH | title = Galpha(14) links a variety of G(i)- and G(s)-coupled receptors to the stimulation of phospholipase C | journal = British Journal of Pharmacology | volume = 132 | issue = 7 | pages = 1431–40 | date = April 2001 | pmid = 11264236 | pmc = 1572686 | doi = 10.1038/sj.bjp.0703933 }}
*{{cite journal | author=Zitzer H, Hönck HH, Bächner D, ''et al.'' |title=Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain. |journal=J. Biol. Chem. |volume=274 |issue= 46 |pages= 32997-3001 |year= 2000 |pmid= 10551867 |doi= }}
* {{cite journal | vauthors = Zatelli MC, Tagliati F, Taylor JE, Rossi R, Culler MD, degli Uberti EC | title = Somatostatin receptor subtypes 2 and 5 differentially affect proliferation in vitro of the human medullary thyroid carcinoma cell line tt | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 5 | pages = 2161–9 | date = May 2001 | pmid = 11344221 | doi = 10.1210/jc.86.5.2161 }}
*{{cite journal | author=Petersenn S, Rasch AC, Presch S, ''et al.'' |title=Genomic structure and transcriptional regulation of the human somatostatin receptor type 2. |journal=Mol. Cell. Endocrinol. |volume=157 |issue= 1-2 |pages= 75-85 |year= 2000 |pmid= 10619399 |doi= }}
* {{cite journal | vauthors = Talme T, Ivanoff J, Hägglund M, Van Neerven RJ, Ivanoff A, Sundqvist KG | title = Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects on adhesion to extracellular matrix components via SSTR2 and/or 3 | journal = Clinical and Experimental Immunology | volume = 125 | issue = 1 | pages = 71–9 | date = July 2001 | pmid = 11472428 | pmc = 1906108 | doi = 10.1046/j.1365-2249.2001.01577.x }}
*{{cite journal | author=Kreienkamp HJ, Zitzer H, Richter D |title=Identification of proteins interacting with the rat somatostatin receptor subtype 2. |journal=J. Physiol. Paris |volume=94 |issue= 3-4 |pages= 193-8 |year= 2001 |pmid= 11087996 |doi= }}
* {{cite journal | vauthors = Klisovic DD, O'Dorisio MS, Katz SE, Sall JW, Balster D, O'Dorisio TM, Craig E, Lubow M | title = Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study | journal = Investigative Ophthalmology & Visual Science | volume = 42 | issue = 10 | pages = 2193–201 | date = September 2001 | pmid = 11527930 | doi =  }}
*{{cite journal | author=Ho MK, Yung LY, Chan JS, ''et al.'' |title=Galpha(14) links a variety of G(i)- and G(s)-coupled receptors to the stimulation of phospholipase C. |journal=Br. J. Pharmacol. |volume=132 |issue= 7 |pages= 1431-40 |year= 2001 |pmid= 11264236 |doi= 10.1038/sj.bjp.0703933 }}
*{{cite journal | author=Zatelli MC, Tagliati F, Taylor JE, ''et al.'' |title=Somatostatin receptor subtypes 2 and 5 differentially affect proliferation in vitro of the human medullary thyroid carcinoma cell line tt. |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue= 5 |pages= 2161-9 |year= 2001 |pmid= 11344221 |doi=  }}
*{{cite journal  | author=Talme T, Ivanoff J, Hägglund M, ''et al.'' |title=Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects on adhesion to extracellular matrix components via SSTR2 and/or 3. |journal=Clin. Exp. Immunol. |volume=125 |issue= 1 |pages= 71-9 |year= 2001 |pmid= 11472428 |doi=  }}
*{{cite journal  | author=Klisovic DD, O'Dorisio MS, Katz SE, ''et al.'' |title=Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study. |journal=Invest. Ophthalmol. Vis. Sci. |volume=42 |issue= 10 |pages= 2193-201 |year= 2001 |pmid= 11527930 |doi=  }}
}}
{{refend}}
{{refend}}


==External links==
== External links ==
* [http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1298 IUPHAR Receptor Database - Somatostatin Receptors]
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2433 | title = Somatostatin Receptors: sst<sub>2</sub> | access-date = | author = | authorlink = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archive-url = | archive-date = | quote = }}
* {{MeshName|somatostatin+receptor+2}}
* {{MeshName|somatostatin+receptor+2}}


{{G protein-coupled receptors}}
{{G protein-coupled receptors}}
{{membrane-protein-stub}}
{{GH/IGF-1 axis signaling modulators}}
{{NLM content}}
{{NLM content}}
[[Category:G protein coupled receptors]]
 
{{WikiDoc Sources}}
[[Category:G protein-coupled receptors]]

Latest revision as of 20:06, 10 December 2018

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Somatostatin receptor type 2 is a protein that in humans is encoded by the SSTR2 gene.[1]

The SSTR2 gene is located on chromosome 17 on the long arm in position 25.1 in humans.[2] It is also found in most other vertebrates.[3]

The somatostatin receptor 2 (SSTR2), which belongs to the G-protein coupled receptor family, is a protein which is most highly expressed in the pancreas (both alpha- and beta-cells), but also in other tissues such as the cerebrum and kidney and in lower amount in the jejunum, colon and liver.[4][5][6] In the pancreas, after binding to somatostatin, it inhibits the secretion of pancreatic enzymes.[4] During development, it stimulates neuronal migration and axon outgrowth.[4]

The somatostatin receptor 2 is expressed in most tumors.[7] Patients with neuroendocrine tumors that over-express the somatostatin receptor 2 have an improved prognosis.[8] The over expression of SSTR2 is tumors can be exploited to selectively deliver radio-peptides to tumors to either detect or destroy them.[9] Somatostatin receptor 2 also has the ability to stimulate apoptosis in many cells including cancer cells.[10] The somatostatin receptor 2 is also being looked at as a possible target in cancer treatment for its ability to inhibit tumor growth.[11]

Function

The gene for somatostatin receptor 2, SSTR2 for short, is responsible for making a receptor for the signalling peptide, somatostatin (SST). Production occurs in the central nervous system, especially the hypothalamus, as well as the digestive system, and pancreas.[12] SSTR2 is a receptor for somatostatin-14 and -28 respectively. The numbers 14 and 28 represent the amount of amino acids in each protein sequence.[12] All somatostatin receptors including SSTR2 may have different specific functions, but all fall under the same receptor super family, the G-protein binding family and all of which are a major inhibitor for other hormones.[13] For all somatostatin inhibitors, somatostatin-14 and -28 work by binding to the receptor with the help of a G-protein. This inhibits adenylyl cyclase and calcium channels. These proteins are released in various parts of the human body and vary in the amount emitted from each organ system. In secretory cells this protein is in a greater volume compared to amount released from activated immune and inflammatory cells. These proteins have a tendency of being emitted in response to items such as: ions, nutrients, neuropeptides, neurotransmitters, hormones, growth factors, and cytokines.[14]

In general, somatostatin can put a cell in cycle arrest using the phosphotyrosine phosphatase dependent regulation of mitrogen-activated protein kinase, this process can lead to a halt in the cell cycle or apoptosis of the cell and is used as a tumor suppressor in the genome. This hormone is also known to perform agonist-dependent endocytosis, which allows a cell to take in receptors, ions, and other molecules.[14]

Because this protein is found in multiple organs, it has a different specific role in each organ or organ system. A major function of the protein made by the gene SSTR2 is pancreatic interaction with the alpha and beta cells. In the delta cells of the pancreas, this hormone inhibits the secretion of both glucagon and insulin in the alpha and beta cells when stimulated by basic nutrients like sugars, proteins, and fats.[15] In fact, this protein, is the dominant one out of all of the somatostatins in the pancreas. In the stomach, it reduces activity of the digestive tract by inhibiting secretion of gastric acid, pepsin, bile, and colonic acid when in the presence of luminal nutrients; all of these secretions are needed for proper digestion. It also represses motor activity in the gut by blocking segmentation of the intestines, gallbladder contraction, and emptying of the bowels.This inhibition by somatostatin allows the body to uptake the maximum amount of nutrients in the digestive system.[16] Along with the gut and pancreas, SSTR2 also inhibits secretion of neurotransmitters in the central and peripheral nervous system. These hormones include dopamine, norpinephrine, thyrotropin-releasing hormone, and corticotropin-releasing hormone. Many of these hormones help the body maintain homeostasis or react properly to a stimulus such as something pleasurable or a stress in the environment. Because of which, the receptors for somatostatin type 2 impact the body's locomotor, sensory, autonomic, and cognitive functions.

Interactions

Somatostatin receptor 2 has been shown to interact with SHANK2.[17]

Clinical significance

The somatostatin hormone itself can negatively affect the uptake of hormones in the body and may play a role in some hormonal conditions. Somatostatin 2 receptors have been found in concentration on the surface of tumor cells, particularly those associated with the neuroendocrine system where the overexpression of somatostatin can lead to many complications[18][19] Due to this, these receptors are considered a prospective aid for the detection of tumors, especially in patients who present with conditions like hypothyroidism and Cushing’s syndrome.[20][21] A synthetic version of the somatostatin hormone, octreotide, has been successfully used in combination with radio-peptide tracers to locate adrenal gland tumors through scintigraphic imaging.[22] A similar method may be utilized to carry and more accurately administer radioactive treatments to tumors.[22] Octreotide and other analogs are preferred for this use due to their possessing of an extended half life compared to the naturally-occurring hormone allowing for more flexibility when used for such treatments.[21]

The association of somatostatin 2 receptors on tumors has also lead to the suggestion of possible alternatives to current tumor treatment methods. The binding of synthetic somatostatin hormones such as octreotide to receptors has been seen to reduce the production of hormones and is now being considered for use in the treatment of some pituitary tumors. One group suggests that the treatment method would be particularly effective against thyrotropin-secreting pituitary adenomas (TSHomas), though further inquiries and clinical trials are needed.[20]

SSTR2 is also being investigated for its potential use as a reporter gene for the visualization of regional gene expression. One study tested this by comparing the PET/CT and light imaging results of laboratory rats’ musculature obtained through the use of a human somatostatin receptor 2 vector and a control luciferase vector.[22] The study suggests that somatostatin receptor genes could be an effective substitute for the current viral-based vectors since the sstr genes elicits less of an immune response and has overall been well-tolerated by the trial patients’ bodies. This form of treatment may be especially useful for the study of gene expression in larger mammals whose larger body mass may obstruct clear visualization of deep tissue areas.[22] The use of sstr2 and sstr5 as biomarkers to track the progress of and treat neuroendocrine tumors displaying circulating tumor cells is also being investigated due to these cells’ somatostatin receptor gene expressivity.[19]

Therapeutic targeting

Most pituitary adenomas express SSTR2, but other somatostatin receptors are also found.[23] Somatostatin analogs (i.e. Octreotide, Lanreotide ) are used to stimulate these receptors, and thus to inhibit further tumor proliferation.[24]

Discovery

There is a group of somatostatin receptors called the somatostatin receptor family. All of the members of the somatostatin receptor family are proteins that sit on the surface of the cell membrane and are responsible for the communication between cells.[25] In 1972,[26] scientists were on the trek to discover more information on the hypothalamus and its "release factors."[26] Studies showed patterns of inhibitory activity of the hypothalamus release factors which led scientists in the direction to discover somatostatin, known as the somatropin release-inhibiting factor, or SRIF. We now know that the SRIF is located at 3q28 (long arm of the third chromosome at the twenty-eighth position) in humans.[26] Peering into location 3q28, the majority of proteins code for the pancreas, ovaries, and prostate along with other components of the endocrine system and nervous system,[27] so it can be drawn that the receptor family has great influence among these systems. The family was first discovered in a segment of a rat's pituitary gland known as the tumor cell line.[28] A cell line is grown as a culture under controlled conditions, so the first discovery was found by culturing these cells in controlled conditions and in an environment outside of its norm. There, researchers found that the tumor cell line expresses a cell dividing inhibitor known as the transforming growth factor beta (TGF-beta) [29] and also acts as an inhibitor to the milk producing hormone in female mammals, prolactin, and growth hormones. Researchers studied the activity of the receptors by conducting an assay with Ligand binding studies,[28] which basically means they were conducting studies to see how prevalent the binding of the receptors occurred.[30][28] Differences in how prevalently they receptors bonded revealed the existence of multiple receptors.[28] Based on the ligand binding affinity and the receptors' signaling mechanisms, the receptor family was divided into 2 different groups, and within those groups, 5 subgroups. The group with a high affinity binding were classified under the SRIF1 group with sst2, sst3, and sst5 in the subgroup, while the receptors with low affinity binding were classified under the SRIF2 group with sst1 and sst4 in the subgroup. Manipulations with the somatostatin receptors are used for many therapies in both the endocrine and nervous system, and now that we know the groups and subgroups of the receptor family, therapy treatment is much more efficient and effective. For example, as you continue reading the article, you will notice the importance and advancements of oncology and tumor treatments, as well as other ways the somatostatin receptors are working and advancing the world of medicine.[31]

The somatostatin receptor 2 is found on the chromosome 17.[32] Information was gathered and determined from a sample of individuals, and conclusions were drawn upon location and other information regarding the SSRT2 protein.[32]

Gene: SSTR2
Title: somatostatin receptor 2
Location: 73,165,021..73,171,955
Length: 6,935 nt
[Positional Info]
NC_000017.11 position: 73,168,608
Gene position: 3,588

Isoforms

Like other proteins, the somatostatin receptor 2 also has variants. Somatostatin receptor 2 exists in two isoforms that are different in carboxy-terimini compositions and size. Alternative splicing of the somatostatin receptor 2 mRNA resulted in two variants, somatostatin receptor 2a (SSTR2A) and somatostatin receptor 2b (SSTR2B). In a rodent, somatostatin receptor 2a is longer compared to the shorter somatostatin receptor 2b. Isoform a and isoform b sequences are different, beginning at the C-terminal regulatory domains.[33] Studies have shown that carboxy-terminal splicing has occurred in many other transmembrane receptors, along with prostaglandin E receptor (EP3).[34] These variants, SST2A receptor and SST2B receptor are seen in some brain and spinal cord areas in a rodent.[35] Somatostatin receptor 2a has a shorter transcript, but is longer then somatostatin receptor 2b and has a unique C- terminus compared to Somatostatin Receptor 2b.[34] SSTRB receptor has approximately 300 nucleotides between carboxyl terminus and transmembrane segments fewer then the original Somatostatin receptor 2. SST2A receptor is made up of 369 amino acids and 346 amino acids make up the SST2B receptor.[36] Somatostatin receptor 2a and somatostatin receptor 2b were found in the medulla oblongata, mesencephalon, testis, cortex, hypothalamus, hippocampus and pituitary of a rodent, using reverse transcription polymerase chain reaction (RT-PCR).[33] Somatostatin receptor 2a is highly evident in the cortex, but the somatostatin receptor 2b is not seen as much. The medeulla oblongata shows equal amounts of the two variants being expressed. The Somatostatin receptor 2a was found mostly in far down layers of the cerebral cortex, in the human brain. This variant of the Somatostatin receptor was found with the use of immunohistochemistry.[37] The difference in ratios of the isoforms imply a tissue-specific control of transcription. Somatostatin receptor 2b is not shown expressed without somatostatin receptor 2a in the brain.[33]

References

  1. ↑ Yamada Y, Stoffel M, Espinosa R, Xiang KS, Seino M, Seino S, Le Beau MM, Bell GI (February 1993). "Human somatostatin receptor genes: localization to human chromosomes 14, 17, and 22 and identification of simple tandem repeat polymorphisms". Genomics. 15 (2): 449–52. doi:10.1006/geno.1993.1088. PMID 8449518.
  2. ↑ "SSTR2 Symbol Report". HUGO Gene Nomenclature Committee.
  3. ↑ "ortholog_gene_6752[group] - Gene". NCBI.
  4. ↑ 4.0 4.1 4.2 Universal protein resource accession number P30874 for "SSTR2 - Somatostatin receptor type 2 - Homo sapiens (Human)" at UniProt.
  5. ↑ "SSTR2 Gene". GeneCards Human Gene Database Gene.
  6. ↑ "SSTR2 somatostatin receptor 2 [Homo sapiens (human)] - Gene". NCBI.
  7. ↑ Reubi JC, Waser B, Schaer JC, Laissue JA (July 2001). "Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands". European Journal of Nuclear Medicine. 28 (7): 836–46. doi:10.1007/s002590100541. PMID 11504080.
  8. ↑ Wang Y, Wang W, Jin K, Fang C, Lin Y, Xue L, Feng S, Zhou Z, Shao C, Chen M, Yu X, Chen J (March 2017). "Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors". Oncology Letters. 13 (3): 1165–1174. doi:10.3892/ol.2017.5591. PMC 5403486. PMID 28454229.
  9. ↑ "SSTR2 - Clinical: Somatostatin Receptor 2 (SSTR2), Immunostain, Technical Component Only". www.mayomedicallaboratories.com. Retrieved 2018-11-10.
  10. ↑ Teijeiro R, Rios R, Costoya JA, Castro R, Bello JL, Devesa J, Arce VM (2002). "Activation of human somatostatin receptor 2 promotes apoptosis through a mechanism that is independent from induction of p53". Cellular Physiology and Biochemistry. 12 (1): 31–8. doi:10.1159/000047824. PMID 11914546.
  11. ↑ Callison JC, Walker RC, Massion PP (2011). "Somatostatin Receptors in Lung Cancer: From Function to Molecular Imaging and Therapeutics". Journal of Lung Cancer. 10 (2): 69–76. doi:10.6058/jlc.2011.10.2.69. PMC 4319675. PMID 25663834.
  12. ↑ 12.0 12.1 Kailey B, van de Bunt M, Cheley S, Johnson PR, MacDonald PE, Gloyn AL, Rorsman P, Braun M (November 2012). "SSTR2 is the functionally dominant somatostatin receptor in human pancreatic β- and α-cells". American Journal of Physiology. Endocrinology and Metabolism. 303 (9): E1107–16. doi:10.1152/ajpendo.00207.2012. PMC 3492856. PMID 22932785.
  13. ↑ "Somatastatin". www.vivo.colostate.edu. Retrieved 2018-11-07.
  14. ↑ 14.0 14.1 Patel YC (July 1999). "Somatostatin and its receptor family". Frontiers in Neuroendocrinology. 20 (3): 157–98. doi:10.1006/frne.1999.0183. PMID 10433861.
  15. ↑ Bhandari S, Watson N, Long E, Sharpe S, Zhong W, Xu SZ, Atkin SL (August 2008). "Expression of somatostatin and somatostatin receptor subtypes 1-5 in human normal and diseased kidney". The Journal of Histochemistry and Cytochemistry. 56 (8): 733–43. doi:10.1369/jhc.2008.950998. PMC 2443611. PMID 18443363.
  16. ↑ Carroll RG (2007). Endocrine System. Elsevier's Integrated Physiology. Elsevier. pp. 157–176. doi:10.1016/b978-0-323-04318-2.50019-4. ISBN 9780323043182.
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  22. ↑ 22.0 22.1 22.2 22.3 Hofmann M, Gazdhar A, Weitzel T, Schmid R, Krause T (December 2006). "PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy". Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 569 (2): 509–11. doi:10.1016/j.nima.2006.08.161.
  23. ↑ Miller GM, Alexander JM, Bikkal HA, Katznelson L, Zervas NT, Klibanski A (April 1995). "Somatostatin receptor subtype gene expression in pituitary adenomas". The Journal of Clinical Endocrinology and Metabolism. 80 (4): 1386–92. doi:10.1210/jcem.80.4.7714115. PMID 7714115.
  24. ↑ Zatelli MC, Ambrosio MR, Bondanelli M, Uberti EC (April 2007). "Control of pituitary adenoma cell proliferation by somatostatin analogs, dopamine agonists and novel chimeric compounds". European Journal of Endocrinology. 156 Suppl 1: S29–35. doi:10.1530/eje.1.02352. PMID 17413185.
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  29. ↑ Yamashita H, Okadome T, Franzén P, ten Dijke P, Heldin CH, Miyazono K (January 1995). "A rat pituitary tumor cell line (GH3) expresses type I and type II receptors and other cell surface binding protein(s) for transforming growth factor-beta". The Journal of Biological Chemistry. 270 (2): 770–4. PMID 7822309.
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  34. ↑ 34.0 34.1 Schulz S, Schmidt H, Händel M, Schreff M, Höllt V (November 1998). "Differential distribution of alternatively spliced somatostatin receptor 2 isoforms (sst2A and sst2B) in rat spinal cord". Neuroscience Letters. 257 (1): 37–40. doi:10.1016/s0304-3940(98)00803-9. PMID 9857960.
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  36. ↑ "Somatostatin receptors". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1616 (1): 1–84. 2003-09-22. doi:10.1016/S0005-2736(03)00235-9. ISSN 0005-2736.
  37. ↑ Cole SL, Schindler M (2000). "Characterisation of somatostatin sst2 receptor splice variants". Journal of Physiology, Paris. 94 (3–4): 217–37. doi:10.1016/S0928-4257(00)00207-2. PMID 11088000.

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