Galanin (2-11) binds to GalR3 in transfected cell lines: limitations for pharmacological definition of receptor subtypes.
The neuropeptide galanin regulates a variety of physiological and pathophysiological processes through three G protein coupled receptors, GalR1, GalR2, and GalR3. The studies on galanin receptor subtype specific effects have been hampered by the lack of high affinity subtype selective antagonist and/or agonist to any of these three galanin receptor subtypes. Since its recent introduction in 2003, galanin (2-11) has been widely used as a GalR2 selective agonist in several in vitro and in vivo studies. In the present paper, we demonstrate that galanin (2-11) binds to rat GalR3 receptors in transfected cell lines with a similar affinity as it binds to GalR2. As none of the available antagonists are galanin receptor subtype selective, as shown here for M35 and M40, more work is needed to confirm whether a galanin (2-11) effect is GalR2 mediated and there is an urgent need for high affinity galanin receptor subtype selective ligands. For now one needs to interpret the data obtained at lower galanin (2-11) concentrations as effects mediated by non-GalR1 type galanin receptors, i.e., GalR2 and/or GalR3.
Lu
Xiaoying
X
Department of Neuropharmacology, The Harold L. Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. xiaoying@scripps.edu
Lundström
Linda
L
Bartfai
Tamas
T
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D019004:Galanin / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008024:Ligands; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044093:Receptor, Galanin, Type 3 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D014162:Transfection
D007457:Iodine Radioisotopes; D008024:Ligands; D010446:Peptide Fragments; D044093:Receptor, Galanin, Type 3; C434734:galanin (2-11)-amide; D019004:Galanin