[D-Trp(34)] neuropeptide Y is a potent and selective neuropeptide YY5 receptor agonist with dramatic effects on food intake

The neuropeptide Y (NPY) Y-5 receptor has been proposed to mediate several physiological effects of NPY, including the potent orexigenic activity of t he peptide. However, the lack of selective NPY Y-5 receptor ligands limits the characterization of the physiological roles of this receptor. Screening of several analogs of NPY revealed that [D-Trp(34)]NPY is a potent and sel ective NPY Y, receptor agonist. Unlike the prototype selective NPY Y-5 rece ptor agonist [D-Trp(32)]NPY, [D-Trp(34)]NPY markedly increases food intake in rats; an effect that is blocked by the selective NPY Y-5 receptor antago nist CGP 71683A. These data demonstrate that [D-Trp(34)]NPY is a useful too l for studies aimed at determining the physiological roles of the NPY Y-5 r eceptor. (C) 2000 Elsevier Science Inc. All rights reserved.