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

• Published in: Regulatory peptides Vol. 102; no. 1; pp. 15 - 19
• Main Authors: Saar, Külliki, Mahlapuu, Riina, Laidmäe, Erki, Valkna, Andres, Kahl, Ulrika, Karelson, Ello, Langel, Ülo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.10.2001; Amsterdam Elsevier
• Subjects: Adenylate cyclase; Adenylyl Cyclases - metabolism; Animals; Binding; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; CHO Cells; Cricetinae; Fundamental and applied biological sciences. Psychology; Galanin; Galanin - antagonists & inhibitors; Galanin - chemistry; Galanin - metabolism; Hippocampus; Hippocampus - metabolism; Humans; Ligands; Neuropeptide Y - analogs & derivatives; Neuropeptide Y - antagonists & inhibitors; Neuropeptide Y - chemistry; Neuropeptide Y - metabolism; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Binding; Rats; Receptor subtypes; Receptor, Galanin, Type 1; Receptor, Galanin, Type 2; Receptors, Galanin; Receptors, Neuropeptide - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Vertebrates: nervous system and sense organs; Binding; Adenylate cyclase; Receptor subtypes; Galanin; Hippocampus; Neuropeptide Y; Galanin receptor; Central nervous system; Subtype; Brain (vertebrata); Chimera
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/S0167-0115(01)00298-1

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.