Pharmacological characterization of neuropeptide Y-(2-36) binding to neuropeptide Y Y1 and Y2 receptors.
Neuropeptide Y-(2-36) has been reported by several research groups to be a more potent orexigenic agent than intact neuropeptide Y. Therefore, it has been proposed that a novel 'Y1 variant' may modulate ingestive behavior. To define the receptor subtype involved in neuropeptide Y-stimulated feeding behavior, we evaluated the binding properties of neuropeptide Y-(2-36) and [125I]neuropeptide Y-(2-36) in established neuropeptide Y1 and Y2 containing cell lines and tissues. Neuropeptide Y-(2-36) displaced [125I]peptide YY binding to SK-N-MC cells (neuropeptide Y Y1 receptors) with a Ki of 3.69 nmol and SK-N-BE(2) cells (neuropeptide Y Y2 receptors) with a Ki of 3.08 nmol. Neuropeptide Y-(2-36) also displaced [125I]peptide YY binding to rat cerebral cortex, hippocampus and olfactory bulb with similar affinities. To examine the brain distribution of [125I]peptide YY, [125I]neuropeptide Y and [125I]neuropeptide Y-(2-36), adjacent sections were labeled and the binding sites detected by autoradiography. A similar distribution of binding was observed for each radioligand in all regions examined. Therefore, neuropeptide Y-(2-36) binds non-selectively to neuropeptide Y Y1 and neuropeptide Y Y2 receptors, but with lower affinity than neuropeptide Y and peptide YY. The increased potency and selectivity seen with neuropeptide Y-(2-36) in feeding studies cannot be explained on the basis of a unique in vitro pharmacology.
Schober
D A
DA
CNS Research, Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN 46285, USA.
Gackenheimer
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SL
Gehlert
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DR
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C083514:neuropeptide Y (2-36); C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor