在大鼠中，神经肽Y（NPY）受体介导的进食的药理学特性表明，Y5亚型比Y1亚型表现更明显，但Y2或Y4亚型则不然。

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

作者信息

Wyss P, Stricker-Krongrad A, Brunner L, Miller J, Crossthwaite A, Whitebread S, Criscione L

机构信息

Metabolic and Cardiovascular Diseases, Novartis Pharma AG, Basle, Switzerland.

出版信息

Regul Pept. 1998 Sep 25;75-76:363-71. doi: 10.1016/s0167-0115(98)00089-5.

DOI:10.1016/s0167-0115(98)00089-5

PMID:9802430

Abstract

Thirteen neuropeptide Y (NPY) agonists were administered intracerebroventricularly (i.c.v.) 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 vivo 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-Trp32]NPY was found to be a Y5-selective ligand and a full agonist in Y5-expressing cells. In vivo, 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.

摘要

向大鼠脑室内注射（i.c.v.）13种神经肽Y（NPY）激动剂（完整剂量-反应曲线），以评估它们对进食的半数有效剂量（ED50）。将这些值与它们在体外对大鼠NPY受体亚型Y1、Y2、Y4和Y5的结合亲和力（IC50）进行比较。体内ED50与体外IC50之间的相关性在Y5受体亚型中很强（r = 0.87；P < 0.01），在Y1受体亚型中较弱（r = 0.48；P < 0.04），而在Y2和Y4受体亚型中无显著相关性。在体外，发现h[D-Trp32]NPY是一种Y5选择性配体，并且在表达Y5的细胞中是一种完全激动剂。在体内，它能剂量依赖性地刺激进食，但未能诱导出与pNPY观察到的完全最大反应。它在禁食24小时的大鼠中不能拮抗pNPY诱导的进食和过度进食。这些发现证明Y5受体亚型，或者可能是Y5与Y1受体亚型联合，而非Y2或Y4受体亚型在进食中起作用。未发现存在另外一种尚未描述的NPY进食受体的证据。