title: Pharmacological characterization and selectivity of the NPY antagonist GR231118 (1229U91) for different NPY receptors.
abstract: Neuropeptide Y (NPY) is widely distributed throughout the central and peripheral nervous system and exerts a wide range of physiological responses by activating specific receptors. In this study we have characterized the potency of the high affinity peptide dimer antagonist, GR231118, to displace radiolabeled NPY/PYY from different tissues and cell lines expressing Y1 or Y2 receptors and from CHO cells stably transfected with human cDNA encoding for Y1, Y2 and Y4 receptors. GR231118 displays high affinity for Y1 and Y4 receptors, equal or better than that of NPY itself, while its activity is several fold weaker for Y2 receptors. Displacement of radiolabeled PYY from rat hypothalamic membranes by GR231118, reveals the existence of high and low affinity binding sites which may be equated to Y1 and Y2 receptors respectively suggesting that the compound maybe used as a tool to dissect central NPY receptors.
authors.affiliation: Department of Metabolic Diseases, Glaxo Wellcome Inc., Research Triangle Park, NC 27709-3398, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Matthews
authors.forename: M
authors.initials: M
authors.lastname: Jansen
authors.forename: D
authors.initials: D
authors.lastname: Lyerly
authors.forename: R
authors.initials: R
authors.lastname: Cox
authors.forename: W J
authors.initials: WJ
authors.lastname: Chen
authors.forename: K J
authors.initials: KJ
authors.lastname: Koller
authors.forename: A J
authors.initials: AJ
authors.lastname: Daniels
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: C097287:1229U91; D018076:DNA, Complementary; D009478:Neuropeptide Y; D010456:Peptides, Cyclic; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C109491:neuropeptide Y4 receptor