Characterization of Somatostatin Receptor Subtypes

Abstract

Somatostatin regulates endocrine and exocrine secretion, possesses antiproliferative properties and acts as a neurotransmitter/neuromodulator in the central nervous system. These effects are mediated by G protein-coupled receptors, of which at least five types have been cloned (sstr1–5). In radioligand-binding studies we have compared the binding properties of sstr1–5 with their activities as somatostatin receptors. All receptors identified so far bind somatostatin-14 and somatostatin-28 with high affinity. The similarities in receptor sequence and in the binding profiles of short synthetic somatostatin analogues such as octreotide, MK 678 or RC 160 for sstr1–5 indicate the existence of two classes of receptors: sstrl/sstr4 with virtually no or very low affinity and sstr2/sstr3/sstr5 with intermediate to high affinity for the short somatostatin analogues. All five receptors mediate inhibition of adenylyl cyclase; this inhibition is sensitive to pertussis toxin. In vitro and in vivo studies suggest the importance of sstr2 and/or sstr5 in the inhibition of growth hormone release. The sstr2 receptor is apparently the predominant subtype expressed in somatostatin receptor-positive tumours. Evidence exists for the importance of sstr5 receptors in insulin secretion and sstr1 receptors in oncology. Somatostatin receptor-selective agonists and antagonists will help to explore new therapeutic opportunities in oncology as well as in endocrine and gastrointestinal disorders and those of the central nervous system.