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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010M1154 – A Novel Galanin Ligand to Delineate theGalaninergic SystemJohan Runesson 1 , Indrek Saar 1,2 , Rannar Sillard 1 , and Ülo Langel 1,21 Department of Neurochemistry, Arrhenius Laboratories for Natural Sciences, StockholmUniversity, Stockholm, SE-10691, Sweden; 2 Laboratory of Molecular Biotechnology,Institute of Technology, University of Tartu, Tartu, 50411, EstoniaIntroductionGalanin was isolated from porcine intestine by Professor Viktor Mutt and colleagues in1983 [1] at the Karolinska Institute in Stockholm. Galanin is a 29 amino acid (30 aminoacid in human) neuropeptide distributed broadly in the brain, spinal cord and gut that hasbeen ascribed involvement in a diversity of physiological actions [2]. Galanin conducts itseffects via three members (GalR1-3) of the G-protein-coupled receptor (GPCR)superfamily. The receptors have distinct distribution patterns and signaling pathways.GalR1 and GalR3 predominantly signal via Gi/o, leading to reduced cAMP-levels, whereasGalR2 mainly signal via Gq/11, leading to inositol phosphate accumulation and an increasein intracellular [Ca 2+ ] (see Figure 1). The galanin-peptide family consists of galanin,galanin message-associated peptide (GMAP), galanin-like peptide (GALP) and alarin. Todistinguish between the three receptor subtypes, GalR1-3, in biological experiments,selective ligands are of great importance, particularly since subtype specific antibodies arenot available [3]. We published in 2009 a novel galanin receptor type 2 (GalR2) selectivechimeric peptide, M1145 [(RG) 2 -N-galanin(2-13)-VL-(P) 3 -(AL) 2 -A-amide]. The M1145peptide showed a more than 90-fold higher affinity for GalR2 over GalR1 and a 76-foldhigher affinity over GalR3 [4]. Here we present preliminary data on receptor binding andthe functional response for a novel galanin receptor selective peptide.Fig. 1. Signaling induced by activation of GalR1-3.452