Characterisation of a new chimeric ligand for galanin receptors: galanin(1-13)-[D-Trp(32)]-neuropeptide Y(25-36) amide

In this work, we studied a novel chimeric peptide, M242, galanin(1-13)-[D-T rp(32)]-neuropeptide Y(25-36)amide, and examined its properties in comparis on with its parent peptide, M32, galanin(1-13)-neuropeptide Y(25-36)amide, a previously known high-affinity li.-and for galanin receptors, and galanin itself. Binding assays performed in Bowes cells known to express human gal anin receptor type I (hGalR1) and in Chinese hamster ovary cells overexpres sing human galanin receptor type 2 (hGalR2) revealed that all three ligands had comparable affinities: at hGalR1 < 1 nM and at hGalR2 < 10 nM. However , in rat hippocampal membranes M242 had a 24-fold lower affinity than galan in (9.4 vs. 0.4 nM) and 134-fold lower affinity than M32 (9.4 vs. 0.07 nM). In the same tissue, we also examined the effects of these peptides on aden ylate cyclase activity. M32 showed a weak antagonistic behaviour but M242 a cted as a potent biphasic regulator of adenylate cyclase. In conclusion, we present and characterise a new peptide M242, which could be a useful tool in studies of galaninergic signalling. (C) 2001 Elsevier Science B.V. All r ights reserved.