CLONING AND EXPRESSIONAL CHARACTERIZATION OF A NOVEL GALANIN RECEPTOR- IDENTIFICATION OF DIFFERENT PHARMACOPHORES WITHIN GALANIN FOR THE 3GALANIN RECEPTOR SUBTYPES

Galanin, a 29-30 amino acid neuropeptide, is found in the central and peripheral nervous systems and displays several important physiologica l activities, The actions are believed to be mediated through distinct G protein-coupled receptors. To date, two galanin receptor subtypes h ave been cloned. In this report, we describe the cloning and expressio n of a cDNA encoding a novel galanin receptor (GalR3). The receptor ha s 370 amino acids and shares 36 and 54% homology with the rat GalR1 an d GalR2 receptors, I-125-Porcine galanin binds the rat GalR3 receptor expressed in COS-7 cells with high affinity (K-d = 0.6 nM) and could b e displaced by galanin and galanin fragments and galanin-chimeric pept ides, The pharmacological profile of this novel receptor is distinct f rom those of GalR1 and GalR2, revealing different pharmacophores withi n galanin for the three galanin receptor subtypes, Northern blot analy sis showed expression in heart, spleen, and testis, Unlike GalR1 and G alR2, no expression of GalR3 was detectable in the brain, suggesting t hat GalR3 may mediate some of the peripheral functions of galanin.