Somatostatin receptor 1, 3, 4, and 5 (SSTR1, SSTR3, SSTR4, SSTR5)

Somatostatin receptors 1, 3, 4, and 5 (SSTR1, SSTR3, SSTR4, SSTR5) are G protein-coupled receptors that mediate the inhibitory physiological actions of the peptide somatostatin [1][2]. These receptors are widely distributed in the brain, pituitary gland, pancreas, and gastrointestinal tract, where they primarily function to suppress the secretion of various hormones and growth factors [2][3]. SSTR1 and SSTR5 play significant roles in regulating growth hormone and insulin secretion, while SSTR3 is uniquely associated with the induction of apoptosis and SSTR4 is involved in modulating inflammatory and nociceptive pathways [1][4]. In oncology and endocrinology, these receptors serve as therapeutic targets for neuroendocrine tumors and pituitary adenomas, especially in patients who do not respond to SSTR2-selective therapies [5][6]. Multi-receptor ligands like pasireotide target these subtypes to provide enhanced control of conditions like Cushing's disease and acromegaly [6][7]. However, the broad inhibitory profile of these receptors, particularly SSTR5, can lead to clinical challenges such as drug-induced hyperglycemia due to the suppression of insulin release [7][8]. Sources: [1] UniProt (P30872, P32745, P31391, P35346) [2] StatPearls: Somatostatin (https://www.ncbi.nlm.nih.gov/books/NBK534832/) [3] IUPHAR/BPS Guide to Pharmacology: Somatostatin receptors (https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=62) [4] Rai et al. (2015) PubMed: 25635015 [5] Gadelha et al. (2017) PubMed: 28405134 [6] Colao et al. (2014) NEJM: 24645851 [7] Schmid et al. (2011) PubMed: 21467163 [8] Henry et al. (2013) PubMed: 23446633

Other names

SST1SST3SST4SST5Somatostatin receptor type 1Somatostatin receptor type 3Somatostatin receptor type 4Somatostatin receptor type 5SS1RSS3RSS4RSS5R

Agonism of G protein-coupled receptors (Gi/o) leading to the inhibition of adenylyl cyclase, reduction of intracellular cAMP levels, and modulation of potassium and calcium channels to inhibit hormone release and cellular proliferation [2][3].