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 receptors have also been cloned from fish tissues. In this study, goldfish sst 5 receptors (gfsst 5 ) 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 [ 1 2 5 I]-LTT-SRIF-28 ([Leu 8 , dTrp 2 2 , 1 2 5 I-Tyr 2 5 ]SRIF-28) and [ 1 2 5 I][Tyr 1 0 ]cortistatin-14 labelled similar receptor densities with high affinity and in a saturable manner (pK d : 9.99-9.71; B m a x : 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 [ 1 2 5 I]LTT-SRIF-28 and [ 1 2 5 I][Tyr 1 0 ]cortistatin-14 correlated significantly (r 2 =0.97, n=20). Pharmacological profiles of human and mouse sst 5 receptors expressed in CCL39 cells correlated markedly less with those of the gfsst 5 profile (r 2 =0.52-0.78, n=<16). Functional expression of the gfsst 5 receptor was examined by measurement of agonist-induced luciferase expression and stimulation of [ 3 5 S]GTPγS ([ 3 5 S]guanosine 5'-O-(3-thiotriphosphate) binding. Profiles were similar to those achieved in radioligand binding studies (r 2 =0.81-0.93, n=20), although relative potency (pEC 5 0 ) was reduced compared to pK d values. Relative efficacy profiles of luciferase expression and [ 3 5 S]GTPγS binding, were rather divergent (r 2 =0.48, n=20) with peptides showing full agonism at one pathway and absence of agonism at the other. BIM 23056 (d-Phe-Phe-Tyr-d-Trp-Lys-Val-Phe-d-Nal-NH 2 ) acted as an antagonist on the effects of SRIF-14 (pK B =6.74+/-0.23) on stimulation of [ 3 5 S]GTPγS binding. Pertussis toxin abolished the effect of SRIF-14 on luciferase expression and [ 3 5 S]GTPγS binding suggesting coupling of the receptor to G i /G o proteins. In summary, the present studies demonstrate that the gfsst 5 receptor has a similar pharmacological profile and transductional properties to mammalian sst 5 receptors. The difference in efficacy profiles defined using different functional assays suggests numerous, agonist specific, conformational receptor states, and/or ligand-dependent receptor trafficking.