PHARMACOLOGICAL CHARACTERIZATION AND SELECTIVITY OF THE NPY ANTAGONIST GR231118 (1229U91) FOR DIFFERENT NPY RECEPTORS

Neuropeptide Y (NPY) is widely distributed throughout the central and peripheral nervous system and exerts a wide range of physiological res ponses by activating specific receptors. In this study we have charact erized the potency of the high affinity peptide dimer antagonist, GR23 1118, to displace radiolabeled NPY/PYY from different tissues and cell lines expressing Y1 or Y2 receptors and from CHO cells stably transfe cted with human cDNA encoding for Y1, Y2 and Y4 receptors. GR231118 di splays high affinity for Y1 and Y4 receptors, equal or better than tha t of NPY itself, while its activity is several fold weaker for Y2 rece ptors. Displacement of radiolabeled PYY from rat hypothalamic membrane s by GR231118, reveals the existence of high and low affinity binding sites which may be equated to Y1 and Y2 receptors respectively suggest ing that the compound maybe used as a tool to dissect central NPY rece ptors. (C) 1997 Elsevier Science B.V.