Somatostatin receptor 2

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. 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. 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. In general, somatostatin can put a cell in cycle arrest using the phosphotyrosine phosphatase dependent regulation of nitrogen-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. 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. Along with the gut and pancreas, SSTR2 also inhibits secretion of neurotransmitters in the central and peripheral nervous system. These hormones include dopamine, norepinephrine, 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. == 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 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. 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. A similar method may be utilized to carry and more accurately administer radioactive treatments to tumors. 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. The association of somatostatin 2 receptors on tumors has also led 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. 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. 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. 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. == Therapeutic targeting ==

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

;Agonists • BIM-23027 • Branosotine • L-054522 • L-779976 • Paltusotine is a promising selective oral once-daily nonpeptide SSTR2 agonist in development as long-term maintenance therapy of acromegaly in adults. == 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. In 1972, scientists were on the trek to discover more information on the hypothalamus and its "release factors." 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. 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) 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, The somatostatin receptor 2 is found on the chromosome 17. Information was gathered and determined from a sample of individuals, and conclusions were drawn upon location and other information regarding the SSRT2 protein. == 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. Studies have shown that carboxy-terminal splicing has occurred in many other transmembrane receptors, along with prostaglandin E receptor (EP3). These variants, SST2A receptor and SST2B receptor are seen in some brain and spinal cord areas in a rodent. Somatostatin receptor 2a has a shorter transcript, but is longer than somatostatin receptor 2b and has a unique C- terminus compared to Somatostatin Receptor 2b. 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). 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. == References ==