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-Trp(32)]-neuropeptide Y(25-36)amide, and examined its properties in comparison with its parent peptide, M32, Galanin(1-13)-neuropeptide Y(25-36)amide, a previously known high-affinity ligand for Galanin receptors, and Galanin itself. Binding assays performed in Bowes cells known to express human Galanin receptor type 1 (hGalR1) and in Chinese hamster ovary cells overexpressing 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 Galanin (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 Adenylate Cyclase activity. M32 showed a weak antagonistic behaviour but M242 acted 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.