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.
Saar
K
K
Department of Neurochemistry and Neurotoxicology, SvanteArrhenius väg 21A, Stockholm University, S-10691, Stockholm, Sweden.
Mahlapuu
R
R
Laidmäe
E
E
Valkna
A
A
Kahl
U
U
Karelson
E
E
Langel U
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019004:Galanin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D008024:Ligands; D009478:Neuropeptide Y; D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D011993:Recombinant Fusion Proteins; C082566:galanin-NPY chimeric peptide M32; D019004:Galanin; D000262:Adenylyl Cyclases