title: 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 somatostastin analogues such as octreotide, MK 678 or RC 160 for sstr1-5 indicate the existence of two classes of receptors sstr1/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.
authors.affiliation: Preclinical Research, SANDOZ Pharma AG, Basle, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Bruns
authors.forename: G
authors.initials: G
authors.lastname: Weckbecker
authors.forename: F
authors.initials: F
authors.lastname: Raulf
authors.forename: H
authors.initials: H
authors.lastname: Lübbert
authors.forename: D
authors.initials: D
authors.lastname: Hoyer
mesh_terms: D000818:Animals; D006801:Humans; D017481:Receptors, Somatostatin / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017481:Receptors, Somatostatin