Somatostatin (sst) Receptors

Somatostatin (somatotropin release inhibiting factor, SRIF) is an endogenous cyclic polypeptide with two biologically active forms. It is an abundant neuropeptide and has a wide range of physiological effects on neurotransmission, secretion and cell proliferation. The somatostatin receptor family consists of five subtypes, sst_1-5, each differentially distributed throughout the central nervous system and periphery. Endogenous somatostatin receptor ligands include somatostatin-14 and somatostatin-28.

Somatostatin receptors have diverse biological functions due to their varied distribution and the fact that they couple to different second messengers - namely adenylyl cyclase, PLC, K⁺ channels and Ca²⁺ channels, amongst others.

Somatostatin receptors in the hypothalamus are involved in the regulation of growth hormone secretion. Other hormones regulated by somatostatin receptors include thyrotropin and prolactin. Somatostatin has antiproliferative effects via stimulation of protein tyrosine phosphatase activity and of the MAPK signaling cascade, with subsequent induction of G₁ cell cycle arrest (sst₁, sst₄, sst₅) and promotion of apoptosis (sst₂, sst₃). It also exhibits antiangiogenic activity via activation of sst₃. Somatostatin regulates neuronal activity by regulating AMPA/kainate-mediated responses to glutamate. Different sst subtypes have opposing effects in this system.

Somatostatin receptors also play a role in blood glucose homeostasis; sst₅ receptors in the pancreatic β-cells stimulate insulin secretion, whilst sst₂ receptors are involved in glucagon secretion from α-cells. In addition, sst₂ receptors inhibit gastric acid secretion and peristalsis in the jejunum. Somatostatin suppresses the release of numerous gastrointestinal hormones, including gastrin, cholecystokinin, secretin and VIP, and consequently plays an integral role in gastrointestinal endocrinology.

External sources of pharmacological information for Somatostatin (sst) Receptors :

• IUPHAR Receptor Code

• BJP Guide

Somatostatin Receptor Gene Data

Somatostatin Receptor Data

* pIC₅₀ values

References

Moller et al (2003) Somatostatin Receptors. Biochem.Biophys.Acta. 1616 1. Alexander et al (2004) Guide to receptors and channels. Br.J.Pharmacol. 141 Suppl.1. Patel and Srikant (1995) Subtype selectivity of peptide analogues for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinology 135 2814. Fenuik et al (2000) Selective somatostatin sst2 receptor blockade with the novel cyclic octapeptide, CYN-154806. Neuropharmacology 39 1443. Rohrer and Schaeffer (2000) Identification and characterization of subtype selective somatostatin receptor agonists. J.Physiol. 94 211.