CHARACTERIZATION OF THE NEUROPEPTIDE-Y RECEPTOR THAT MEDIATES FEEDINGIN THE RAT - A ROLE FOR THE Y5 RECEPTOR

Food intake was measured in freely fed rats following intracerebrovent ricular administration of neuropeptide Y (NPY) and several of its anal ogues and antagonists to investigate the hypothesis that the NPY Y5 re ceptor mediates feeding. Rat NPY (rNPY), rNPY(2-36) and rNPY(3-36) pro duced similar feeding responses over the dose range 0.7-7.0 nmol. Rat peptide YY (rPYY) was more potent and at least as efficacious as rNPY. [Leu31 Pro34]-rNPY (agonist potency: Y1 > Y5 > Y4 = y6) and human pan creatic polypeptide (hPP) produced flatter dose-response curves, sugge sting partial agonism at the receptor(s). rNPY(13-36) (agonist potency : Y2 > Y5) had little activity and rPP was inactive. [D-Trp32]-NPY was a weak orexigenic agent given alone and, consistent with partial agon ism, it markedly antagonised the response to porcine NPY (pNPY). Simil arly, the receptor antagonist (Y1 > Y4) 1229U91 stimulated feeding sli ghtly, and markedly inhibited rNPY-induced feeding. In contrast to a p revious report, BIBP 3226 (70 nmol), another YI receptor antagonist, f ailed to inhibit the response to rNPY. Our data in vivo are inconsiste nt with findings that hPP, [Leu31 Pro34]-rNPY and [D-Trp32]-rNPY are f ull agonists at the rat cloned Y5 receptor. Thus, whilst the Y5 recept or may be involved, its participation as the sole receptor mediating t he orexigenic action of NPY in the rat remains unproven. (C) 1998 Else vier Science B.V. All rights reserved.