TY - JOUR T1 - Somatostatin<sub>5</sub> Receptor-Mediated [<sup>35</sup>S]Guanosine-5′-<em>O</em>-(3-thio)triphosphate Binding: Agonist Potencies and the Influence of Sodium Chloride on Intrinsic Activity JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1060 LP - 1069 DO - 10.1124/mol.51.6.1060 VL - 51 IS - 6 AU - Andrea J. Williams AU - Anton D. Michel AU - Wasyl Feniuk AU - Patrick P. A. Humphrey Y1 - 1997/06/01 UR - http://molpharm.aspetjournals.org/content/51/6/1060.abstract N2 - We studied the activation of the human somatostatin5receptor recombinantly expressed in CHO-K1 cells by using some newly available agonists and antagonists. Somatostatin-28 bound to this receptor with a higher affinity than somatostatin-14 and was more potent in increasing [35S]guanosine-5′-O-(3-thio)triphosphate ([35S]GTPγS) binding. Somatostatin-14-induced [35S]GTPγS binding to membranes from this cell line was decreased in a concentration-related manner by increasing concentrations of GDP and sodium chloride. At 50 mm (low) sodium, agonist EC50 values for stimulating [35S]GTPγS binding were lower than those at 150 mm (high) sodium and were closer to their respective affinity estimates (dissociation equilibrium constants) for binding to the receptor in the absence of sodium. Both agonist binding to the high affinity state of the receptor and agonist-induced [35S]GTPγS binding were abolished by pertussis toxin pretreatment. The putative somatostatin5 receptor-selective ligand L-362,855, unlike somatostatin-14 and somatostatin-28, showed differential intrinsic activity for stimulation of [35S]GTPγS binding, behaving as a partial agonist in high sodium and a full agonist in low sodium. In contrast, BIM-23056 did not behave as an agonist under any conditions studied but was able to antagonize somatostatin-14-induced [35S]GTPγS binding. We conclude that measurement of [35S]GTPγS binding mediated by somatostatin receptor activation in the presence of different concentrations of sodium chloride provides a useful functional assay for assessing the relative agonist efficacies of novel ligands identified from radioligand binding studies. ER -