title: Neuropeptide Y 3-36 is an endogenous ligand selective for Y2 receptors.
abstract: Neuropeptide Y (NPY 1-36) binds to Y1 and Y2 receptors with similar affinity. No endogenous molecular form of NPY with selectivity for Y1 or Y2 receptors has been described so far. We report the presence of an endogenous fragment of NPY in porcine brain, NPY 3-36, which lacks the amino-terminal dipeptide Tyr-Pro of NPY 1-36. NPY 3-36 accounts for 35% of NPY-like immunoreactivity in porcine brain. We have compared binding of NPY 3-36 and NPY 1-36 in model systems of Y1-like (SK-N-MC cells) and Y2-like receptors (CHP234 cells). NPY 3-36 and NPY 1-36 had similarly high affinity for Y2-like receptors on CHP234 cells, but NPY 3-36 had a 1000-fold lower affinity than NPY 1-36 for Y1-like receptors on SK-N-MC cells. Thus amino-terminal cleavage of NPY 1-36 generating NPY 3-36 converts an unselective Y1/Y2 receptor ligand into a highly Y2 selective ligand. This may be a means of fine tuning NPY biological actions.
authors.affiliation: Department of Medicine, University of Essen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Grandt
authors.forename: M
authors.initials: M
authors.lastname: Schimiczek
authors.forename: W
authors.initials: W
authors.lastname: Rascher
authors.forename: F
authors.initials: F
authors.lastname: Feth
authors.forename: J
authors.initials: J
authors.lastname: Shively
authors.forename: T D
authors.initials: TD
authors.lastname: Lee
authors.forename: M T
authors.initials: MT
authors.lastname: Davis
authors.forename: J R
authors.initials: JR
authors.lastname: Reeve
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D017421:Sequence Analysis; D013552:Swine
chemical_list: D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor