1.Pharmacological characterisation of the goldfish somatostatin sst5 receptor.
Nunn C;Feuerbach D;Lin X;Peter R;Hoyer D Eur J Pharmacol. 2002 Feb 2;436(3):173-86.
Somatostatin (somatotropin release inhibiting factor, SRIF), exerts its effects via specific G protein coupled receptors of which five subtypes have been cloned (sst1-5). Recently, SRIF receptors have also been cloned from fish tissues. In this study, goldfish sst5 receptors (gfsst5) were expressed and characterised in the Chinese hamster lung fibroblast cell line, that harbours the luciferase reporter gene driven by the serum responsive element (CCL39-SRE-Luci). The agonist radioligands [125I]-LTT-SRIF-28 ([Leu8, DTrp22, 125I-Tyr25]SRIF-28) and [125I][Tyr10]cortistatin-14 labelled similar receptor densities with high affinity and in a saturable manner (pKd: 9.99-9.71; Bmax: 300-350 fmol mg-1). 5'-Guanylyl-imidodiphosphate inhibited radioligand binding to some degree (38.5-57.9%). In competition binding studies, the pharmacological profile of SRIF binding sites defined with [125I]LTT-SRIF-28 and [125I][Tyr10]cortistatin-14 correlated significantly (r2=0.97, n=20). Pharmacological profiles of human and mouse sst5 receptors expressed in CCL39 cells correlated markedly less with those of the gfsst5 profile (r2=0.52-0.78, n > or = b16). Functional expression of the gfsst5 receptor was examined by measurement of agonist-induced luciferase expression and stimulation of [35S]GTPgammaS ([35S]guanosine 5'-O-(3-thiotriphosphate) binding.
2.Specific inhibition of rat pancreatic insulin or glucagon release by receptor-selective somatostatin analogs.
Rossowski WJ;Coy DH Biochem Biophys Res Commun. 1994 Nov 30;205(1):341-6.
A group of new peptide ligands displaying high selectivity for binding to somatostatin receptor subtypes 2, 3 or 5 have been used to characterize somatostatin receptor involvement in the inhibition of glucagon secretion in rats. It was found that NC-8-12 and DC-25-100, which have high affinity for SSTR2 and much less affinity for the type 5 receptor, were by far the most potent inhibitors of glucagon secretion with EC50s of 48 and 18 nmole, respectively, relative to somatostatin itself (EC50 131 nmole). These two analogs were actually much less potent than somatostatin in inhibiting glucose-stimulated insulin release. In contrast, DC-23-99 (a type 5 receptor selective analog), which was previously found to be a more potent inhibitor of insulin secretion than somatostatin, had considerably less potent (EC50 410 nmole) effects on glucagon release. The SSTR3-specific ligands, DC-25-12 and DC-25-20, were not effective at the doses tested. The differing spectra of activities of these analogs suggest that inhibition of insulin and glucagon secretion in rats is mediated by entirely different somatostatin receptor populations.
3.Potent inhibitory effects of a type four receptor-selective somatostatin analog on rat insulin release.
Rossowski WJ;Coy DH Biochem Biophys Res Commun. 1993 Dec 15;197(2):366-71.
A total of 5 somatostatin (SS) receptors have been characterized, cloned, and transfected into various cell types which have recently been used to discern peptide ligands displaying high degrees of selectivity for binding to types 2, 3, and 4. These have now allowed us to examine which receptor(s) is involved in SS inhibition of glucose-stimulated rat pancreatic insulin release. The type 4 selective ligand, DC-23-99, which had little affinity for receptor types 1, 2, or 5, was at least equipotent to SS in preventing insulin release. In contrast, the type 3 selective peptide, DC-25-20, was totally devoid of inhibitory effects. Peptides, such as NC-8-12, which have extremely high affinity for type 2 receptors but far less for types 1, 3, 4 and 5, were considerably less potent than SS in this assay. Thus, 2 major inhibitory physiological functions of SS on GH (type 2) and insulin release appear to be mediated by entirely different receptor types.
