The pharmacology of neuropeptide Y (NPY) receptor-mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes

被引:74
作者
Wyss, P [1 ]
Stricker-Krongrad, A [1 ]
Brunner, L [1 ]
Miller, J [1 ]
Crossthwaite, A [1 ]
Whitebread, S [1 ]
Criscione, L [1 ]
机构
[1] Novartis Pharma AG, Metab & Cardiovasc Dis, CH-4002 Basel, Switzerland
关键词
obesity; eating disorders; agonist; food intake; hyperphagia; peptides;
D O I
10.1016/S0167-0115(98)00089-5
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thirteen neuropeptide Y (NPY) agonists were administered intracerebroventricularly (icv) in rats (full dose-response curves) to estimate their half-effective dose (ED50) on feeding. These values were compared to their binding affinities (IC50) for rat NPY receptor subtypes Y1, Y2, Y4 and Y5 in vitro. Correlations between in vive ED50 and in vitro IC50 were strong for the Y5 (r = 0.87; P < 0.01), weak for the Y1 (r = 0.48; P < 0.04) and non-significant for the Y2 and Y4 receptor subtypes. In vitro, h[D-Trp(32)]NPY was found to be a YS-selective ligand and a full agonist in YS-expressing cells. In vive, it dose-dependently stimulated feeding, but failed to induce the full maximal response observed with pNPY. It did not antagonize pNPY-induced feeding and overfeeding in 24 h fasted rats. These findings demonstrate a role for the Y5, or possibly Y5 in combination with Y1, but not Y2 or Y4 receptor subtypes in feeding. No evidence was found for the existence of an additional, as yet undescribed, NPY feeding receptor. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:363 / 371
页数:9
相关论文
共 48 条
[11]  
Gehlert DR, 1996, MOL PHARMACOL, V49, P224
[12]   EXPRESSION CLONING AND PHARMACOLOGICAL CHARACTERIZATION OF A HUMAN HIPPOCAMPAL NEUROPEPTIDE-Y PEPTIDE YY Y2 RECEPTOR SUBTYPE [J].
GERALD, C ;
WALKER, MW ;
VAYSSE, PJJ ;
HE, CG ;
BRANCHEK, TA ;
WEINSHANK, RL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) :26758-26761
[13]   A receptor subtype involved in neuropeptide-Y-induced food intake [J].
Gerald, C ;
Walker, MW ;
Criscione, L ;
Gustafson, EL ;
BatzlHartmann, C ;
Smith, KE ;
Vaysse, P ;
Durkin, MM ;
Laz, TM ;
Linemeyer, DL ;
Schaffhauser, AO ;
Whitebread, S ;
Hofbauer, KG ;
Taber, RI ;
Branchek, TA ;
Weinshank, RL .
NATURE, 1996, 382 (6587) :168-171
[14]   Cloning and characterization of a novel receptor to pancreatic polypeptide, a member of the neuropeptide Y receptor family [J].
Gregor, P ;
Millham, ML ;
Feng, Y ;
DeCarr, LB ;
McCaleb, ML ;
Cornfield, LJ .
FEBS LETTERS, 1996, 381 (1-2) :58-62
[15]  
HAYNES AC, 1997, INT J OBESITY REL ME, V21, pS16
[16]   Identification of a novel hypothalamic neuropeptide Y receptor associated with feeding behavior [J].
Hu, YH ;
Bloomquist, BT ;
Cornfield, LJ ;
DeCarr, LB ;
FloresRiveros, JR ;
Friedman, L ;
Jiang, PL ;
LewisHiggins, L ;
Sadlowski, Y ;
Schaefer, J ;
Velazquez, N ;
McCaleb, ML .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (42) :26315-26319
[17]   RECEPTORS FOR PEPTIDE YY AND NEUROPEPTIDE-Y ON GUINEA-PIG PANCREATIC ACINI [J].
HUANG, SC ;
TSAI, MF .
PEPTIDES, 1994, 15 (03) :405-410
[18]   INVIVO STRUCTURE ACTIVITY STUDY SUPPORTS THE EXISTENCE OF HETEROGENEOUS NEUROPEPTIDE-Y RECEPTORS [J].
JOLICOEUR, FB ;
MICHAUD, JN ;
MENARD, D ;
FOURNIER, A .
BRAIN RESEARCH BULLETIN, 1991, 26 (02) :309-311
[19]   STRUCTURE-FUNCTION ANALYSIS OF STIMULATION OF FOOD-INTAKE BY NEUROPEPTIDE-Y - EFFECTS OF RECEPTOR AGONISTS [J].
KALRA, SP ;
DUBE, MG ;
FOURNIER, A ;
KALRA, PS .
PHYSIOLOGY & BEHAVIOR, 1991, 50 (01) :5-9
[20]  
KRAUSE J, 1992, MOL PHARMACOL, V41, P817