Pharmacological characterisation of the goldfish somatostatin sst5 receptor

摘要: Abstract Somatostatin (somatotropin release inhibiting factor, SRIF), exerts its effects via specific G protein coupled receptors of which five subtypes have been cloned (sst 1–5 ). Recently, SRIF also from fish tissues. In this study, goldfish sst 5 (gfsst ) were expressed and characterised in the Chinese hamster lung fibroblast cell line, that harbours luciferase reporter gene driven by serum responsive element (CCL39-SRE-Luci). The agonist radioligands [ 125 I]-LTT-SRIF-28 ([Leu 8 , d Trp 22 I-Tyr 25 ]SRIF-28) I][Tyr 10 ]cortistatin-14 labelled similar receptor densities with high affinity a saturable manner (p K : 9.99–9.71; B max 300–350 fmol mg −1 5′-Guanylyl-imidodiphosphate inhibited radioligand binding to some degree (38.5–57.9%). competition studies, pharmacological profile sites defined I]LTT-SRIF-28 correlated significantly ( r 2 =0.97, n =20). Pharmacological profiles human mouse CCL39 cells markedly less those gfsst =0.52–0.78, ≥16). Functional expression was examined measurement agonist-induced stimulation 35 S]GTPγS ([ S]guanosine 5′- O -(3-thiotriphosphate) binding. Profiles achieved studies =0.81–0.93, =20), although relative potency (pEC 50 reduced compared p values. Relative efficacy binding, rather divergent =0.48, =20) peptides showing full agonism at one pathway absence other. BIM 23056 -Phe-Phe-Tyr- -Trp-Lys-Val-Phe- -Nal-NH acted as an antagonist on SRIF-14 =6.74±0.23) Pertussis toxin abolished effect suggesting coupling i /G o proteins. summary, present demonstrate has transductional properties mammalian receptors. difference using different functional assays suggests numerous, specific, conformational states, and/or ligand-dependent trafficking.