Somatostatin (somatotropin release inhibiting factor) is an abundant neuropeptide, which acts on five subtypes of somatostatin receptor (SST₁-SST₅; nomenclature as agreed by the NC-IUPHAR Subcommittee on Somatostatin Receptors [9]). Activation of these receptors produces a wide range of physiological effects throughout the body including the inhibition of secretion of many hormones. Endogenous ligands for these receptors are somatostatin-14 (SRIF-14 (SST, P61278)) and somatostatin-28 (SRIF-28 (SST, P61278)). Cortistatin-14 has also been suggested to be an endogenous ligand for somatostatin receptors [5].

[¹²⁵I]Tyr¹¹-SRIF-14, [¹²⁵I]LTT-SRIF-28, [¹²⁵I]CGP 23996 and [¹²⁵I]Tyr¹⁰-CST14 may be used to label somatostatin receptors nonselectively. A number of nonpeptide subtype-selective agonists have been synthesised [17]. Octreotide and lanreotide are being used in the treatment of SST₂-expressing neuroendocrine tumors and pasireotide for SST₅-expressing neuroendocrine tumors. A novel peptide somatostatin analogue, veldoreotide (COR-005), has affinity for SST₂, SST₄ and SST₅ receptors and is a potent inhibitor of GH secretion [16,19].

* Key recommended reading is highlighted with an asterisk

* Colao A, Auriemma RS, Lombardi G, Pivonello R. (2011) Resistance to somatostatin analogs in acromegaly. Endocr. Rev., 32 (2): 247-71. [PMID:21123741]

Durán-Prado M, Malagón MM, Gracia-Navarro F, Castaño JP. (2008) Dimerization of G protein-coupled receptors: new avenues for somatostatin receptor signalling, control and functioning. Mol. Cell. Endocrinol., 286 (1-2): 63-8. [PMID:18242821]

* Hoyer D, Epelbaum J, Feniuk W, Humphrey PPA, Meyerhof W, O'Carroll AM et al.. (2000) Somatostatin receptors. In The IUPHAR Compendium of Receptor Characterization and Classification, 2nd edn. Edited by Watson SP, Girdlestone D (IUPHAR Media) 354-364.

* Schulz S, Lehmann A, Kliewer A, Nagel F. (2014) Fine-tuning somatostatin receptor signalling by agonist-selective phosphorylation and dephosphorylation: IUPHAR Review 5. Br. J. Pharmacol., 171 (7): 1591-9. [PMID:24328848]

* Weckbecker G, Lewis I, Albert R, Schmid HA, Hoyer D, Bruns C. (2003) Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov, 2 (12): 999-1017. [PMID:14654798]

1. Afargan M, Janson ET, Gelerman G, Rosenfeld R, Ziv O, Karpov O, Wolf A, Bracha M, Shohat D, Liapakis G et al.. (2001) Novel long-acting somatostatin analog with endocrine selectivity: potent suppression of growth hormone but not of insulin. Endocrinology, 142 (1): 477-86. [PMID:11145612]

2. Bruns C, Raulf F, Hoyer D, Schloos J, Lubbert H, Weckbecker G. (1996) Binding properties of somatostatin receptor subtypes. Metabolism, 45: 17-20. [PMID:8769372]

3. Castro SW, Buell G, Feniuk W, Humphrey PP. (1996) Differences in the operational characteristics of the human recombinant somatostatin receptor types, sst1 and sst2, in mouse fibroblast (Ltk-) cells. Br. J. Pharmacol., 117 (4): 639-46. [PMID:8646408]

4. Cescato R, Erchegyi J, Waser B, Piccand V, Maecke HR, Rivier JE, Reubi JC. (2008) Design and in vitro characterization of highly sst2-selective somatostatin antagonists suitable for radiotargeting. J. Med. Chem., 51 (13): 4030-7. [PMID:18543899]

5. De Lecea L, Criado JR, Prospero-Garcia O, Gautvik KM, Schweitzer P, Danielson PE, Dunlop CL, Siggins GR, Henriksen SJ, Sutcliffe JG. (1996) A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature, 381: 242-245. [PMID:8622767]

6. Engstrom M, Tomperi J, El-Darwish K, Ahman M, Savola JM, Wurster S. (2005) Superagonism at the human somatostatin receptor subtype 4. J Pharmacol Exp Ther, 312: 332-338. [PMID:15333679]

7. Erchegyi J, Hoeger CA, Low W, Hoyer D, Waser B, Eltschinger V, Schaer JC, Cescato R, Reubi JC, Rivier JE. (2005) Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan. J Med Chem, 48: 507-514. [PMID:15658864]

8. Farb TB, Adeva M, Beauchamp TJ, Cabrera O, Coates DA, Meredith TD, Droz BA, Efanov A, Ficorilli JV, Gackenheimer SL et al.. (2017) Regulation of Endogenous (Male) Rodent GLP-1 Secretion and Human Islet Insulin Secretion by Antagonism of Somatostatin Receptor 5. Endocrinology, 158 (11): 3859-3873. [PMID:28938487]

9. Günther T, Tulipano G, Dournaud P, Bousquet C, Csaba Z, Kreienkamp HJ, Lupp A, Korbonits M, Castaño JP, Wester HJ et al.. (2018) International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature. Pharmacol. Rev., 70 (4): 763-835. [PMID:30232095]

10. He S, Ye Z, Truong Q, Shah S, Du W, Guo L, Dobbelaar PH, Lai Z, Liu J, Jian T et al.. (2012) The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes. ACS Med Chem Lett, 3 (6): 484-9. [PMID:24900499]

11. Hoyer D, Nunn C, Hannon J, Schoeffter P, Feuerbach D, Schuepbach E, Langenegger D, Bouhelal R, Hurth K, Neumann P, Troxler T, Pfaeffli P. (2004) SRA880, in vitro characterization of the first non-peptide somatostatin sst(1) receptor antagonist. Neurosci Lett, 361: 132-135. [PMID:15135911]

12. Hoyer D, Vassout A, Gentsch C, Enz A, Vigouret JM, Jaton A, Schoeffter P, Kelly P, Wrynn A, Hurth K, Troxler T. (2004) Functional characterization of NVP ACQ090, a somatostatin sst₃ receptor antagonist. Soc Neuroscience Abs,: -.

13. Liu S, Tang C, Ho B, Ankersen M, Stidsen CE, Crider AM. (1998) Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas. J Med Chem, 41: 4693-4705. [PMID:9822540]

14. Meyerhof W. (1998) The elucidation of somatostatin receptor functions: a current view. Rev Physiol Biochem Pharmacol, 133: 55-108. [PMID:9600011]

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16. Plöckinger U, Hoffmann U, Geese M, Lupp A, Buchfelder M, Flitsch J, Vajkoczy P, Jakob W, Saeger W, Schulz S et al.. (2012) DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours. Eur. J. Endocrinol., 166 (2): 223-34. [PMID:22065857]

17. Rohrer SP, Birzin ET, Mosley RT, Berk SC, Hutchins SM, Shen DM, Xiong Y, Hayes EC, Parmar RM, Foor F, Mitra SW, Degrado SJ, Shu M, Klopp JM, Cai SJ, Blake A, Chan WW, Pasternak A, Yang L, Patchett AA, Smith RG, Chapman KT, Schaeffer JM. (1998) Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science, 282: 737-740. [PMID:9784130]

18. Schmid HA, Schoeffter P. (2004) Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors. Neuroendocrinology, 80: 47-50. [PMID:15477717]

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20. Siehler S, Seuwen K, Hoyer D. (1998) [125I]Tyr10-cortistatin14 labels all five somatostatin receptors. Naunyn Schmiedebergs Arch Pharmacol, 357: 483-489. [PMID:9650799]

21. Siehler S, Seuwen K, Hoyer D. (1998) [125I][Tyr3]octreotide labels human somatostatin sst2 and sst5 receptors. Eur J Pharmacol, 348: 311-320. [PMID:9652348]

22. Siehler S, Seuwen K, Hoyer D. (1999) Characterisation of human recombinant somatostatin receptors. 1. Radioligand binding studies. Naunyn Schmiedebergs Arch Pharmacol, 360: 488-499. [PMID:10598788]

23. Yang L, Berk SC, Rohrer SP, Mosley RT, Guo L, Underwood DJ, Arison BH, Birzin ET, Hayes EC, Mitra SW, Parmar RM, Cheng K, Wu TJ, Butler BS, Foor F, Pasternak A, Pan Y, Silva M, Freidinger RM, Smith RG, Chapman K, Schaeffer JM, Patchett AA. (1998) Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2. Proc Natl Acad Sci U S A, 95: 10836-10841. [PMID:9724791]

Subcommittee members: Stefan Schulz (Chairperson) Department of Pharmacology and Toxicology University Hospital Friedrich Schiller University Jena Germany Corinne Bosquet INSERM U531 Institut Louis Bugnard CHU Rangueil Toulouse cedex 4 France Justo Castano Department of Cell Biology, Physiology and Immunology Edificio Severo Ochoa. Planta 3 Campus de Rabanales University of Cordoba E-14014 Córdoba Spain Micheal Culler IPSEN 27 Maple Street Milford 01757 MA USA Jacques Epelbaum Institut National de la Sante de la Recherche Medicale INSERM- UNIVERSITE PARIS DESCARTES UMR. 549 2 ter rue d'Alesia Paris F-75014 France Leo Hofland Division of Endocrinology Department of Internal Medicine Erasmus Medical Center Molewaterplein 50 3015 GE Rotterdam The Netherlands Daniel Hoyer (Past chairperson) Chair and Head Department of Pharmacology and Therapeutics School of Medicine Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne Parkville Victoria 3010 Australia Jean-Claude Reubi Institute of Pathology University of Berne Murtenstrasse 31 Berne CH-3010 Switzerland Herbert Schmid Novartis Pharma AG Novartis Institutes for Biomedical Research Oncology CH-4057 Basel Switzerland Agnes Schonbrunn Department of Pharmacology The University of Texas Medical School PO Box 20708 6431 Fannin Houston TX 77225 USA

Other contributors: Wasyl Feniuk Glaxo Institute of Applied Pharmacology University of Cambridge Department of Pharmacology Tennis Court Road Cambridge CB2 1QJ UK Anthony Harmar (1951-2014) formerly of the University of Edinburgh, Edinburgh, Scotland Rebecca Hills (Past curator) Patrick P. A. Humphrey Glaxo Institute of Applied Pharmacology Department of Pharmacology University of Cambridge Tennis Court Road Cambridge CB2 1QJ UK Wolfgang Meyerhof Department of Molecular Genetics German Institute of Human Nutrition Arthur-Scheunert-Allee 114-116 Potsdam-Rehbruecke D-14558 Germany Anne-Marie O'Carroll Bristol Royal Infirmary University of Bristol Malborough Street Bristol BS2 8HW UK Yogesh C. Patel Department of Medicine McGill University Royal Victoria Hospital Room M3.15 687 Pine Avenue West Montréal Québec H3A 1A1 Canada Terry Reisine ActiveSite Biotech La Jolla CA USA Marcus Schindler Boehringer Ingelheim Pharma Department of Cardiovascular and MetabolicResearch Biberach D-88397 Germany John E. Taylor Biomeasure 27 Maple Street Milford MA 01757-3650 USA Annamaria Vezzani Department of Neuroscience Istituto di Ricerche Farmacologiche 'Mario Negri' Via Eritrea 62 Milan 20157 Italy