Somatostatin Receptor 5 Antibodies

The somatostatin receptor subtype 5 (SST5, SSTR5) is a class A G protein-coupled receptor (GPCR) that is activated by the endogenous peptides somatostatin-14 and somatostatin-28. SST5 primarily couples to Gi/o proteins, leading to inhibition of adenylyl cyclase, reduced intracellular cAMP levels, modulation of calcium and potassium channels, and activation of MAPK- and phosphotyrosine phosphatase-dependent signaling pathways. The receptor is highly expressed in the anterior pituitary, pancreatic islets, gastrointestinal tract, adrenal gland, and hypothalamus, and is frequently overexpressed in pituitary adenomas and neuroendocrine tumors. Functionally, SST5 plays a major role in the inhibition of hormone secretion, particularly growth hormone, adrenocorticotropic hormone (ACTH), insulin, glucagon, and gastrointestinal peptides, and it also contributes to the regulation of cell proliferation and apoptosis. SST5 is an important therapeutic target for endocrine disorders, especially acromegaly and Cushing's disease. Several clinically approved somatostatin analogs interact with SST5, including pasireotide, which displays the highest affinity for this receptor subtype and is approved for the treatment of acromegaly and Cushing's disease. In contrast, octreotide and lanreotide primarily target SST2 but also exhibit moderate affinity for SST5. In addition, selective experimental SST5 agonists such as L-817,818 and BIM-23268 have been widely used to investigate SST5 pharmacology, although no SST5-selective agonist has yet been approved for clinical use. Thus, it is the primary target for pasireotide (Signifor) which is the first line medical treatment for adrenocorticotropic hormone (ACTH)-producing adenomas (Cushing’s disease). SST5 desensitization and internalization are regulated by phosphorylation of carboxyl-terminal threonine333 (pT333-SST5). Threonine347 is constitutively phosphorylated in the absence of agonist. This nomenclature refers to the human SST5. Agonist-induced phosphorylation of T333 is mediated by GRK2. SST5 dephosphorylation is primarily mediated by protein phosphatase 1 gamma (PP1γ). For more information on SST5 pharmacology please refer to the IUPHAR database. For further reading refer to:

Petrich A, Mann A, Kliewer A, Nagel F, Strigli A, Märtens JC, Pöll F, Schulz S. Phosphorylation of threonine 333 regulates trafficking of the human sst5 somatostatin receptor. Mol Endocrinol. 2013 Apr;27(4):671-82. doi: 10.1210/me.2012-1329. Epub 2013 Feb 15. PubMed PMID: 23418396; PubMed Central PMCID: PMC5416807.

Lehmann A, Kliewer A, Märtens JC, Nagel F, Schulz S. Carboxyl-terminal receptor domains control the differential dephosphorylation of somatostatin receptors by protein phosphatase 1 isoforms. PLoS One. 2014 Mar 17;9(3):e91526. doi: 10.1371/journal.pone.0091526. eCollection 2014. PubMed PMID: 24637622; PubMed Central PMCID: PMC3956607.

Kliewer A, Mann A, Petrich A, Pöll F, Schulz S. A transplantable phosphorylation probe for direct assessment of G protein-coupled receptor activation. PLoS One. 2012;7(6):e39458. doi: 10.1371/journal.pone.0039458. Epub 2012 Jun 26. PubMed PMID: 22745760; PubMed Central PMCID: PMC3383726.