对CGP 71683A作出反应时食物摄入量减少可能是由于除NPY Y5受体阻断以外的机制。

Reduced food intake in response to CGP 71683A may be due to mechanisms other than NPY Y5 receptor blockade.

作者信息

Della Zuana O, Sadlo M, Germain M, Félétou M, Chamorro S, Tisserand F, de Montrion C, Boivin J F, Duhault J, Boutin J A, Levens N

机构信息

Metabolic Diseases, Institut de Recherches Servier, Suresnes, France.

出版信息

Int J Obes Relat Metab Disord. 2001 Jan;25(1):84-94. doi: 10.1038/sj.ijo.0801472.

DOI:10.1038/sj.ijo.0801472

PMID:11244462

Abstract

INTRODUCTION

The purpose of this study was to test the continuing validity of the hypothesis that neuropeptide Y (NPY) produced in the brain controls food intake through an interaction with the NPY Y(5) receptor subtype.

METHODS

The hypothesis was tested using CGP 71683A a potent and highly selective non-peptide antagonist of the NPY Y(5) receptor which was administered into the right lateral ventricle of obese Zucker fa/fa rats.

RESULTS

Intraventricular injection of 3.4 nmol/kg NPY increased food intake during a 2 h test period. Doses of CGP 71683A in excess of 15 nmol/kg (i.cv.) resulted in blockade of the increase in food intake produced by NPY. Repeated daily injection of CGP 71683A (30--300 nmol/kg, i.cv.) immediately before the dark phase produced a dose-dependent and slowly developing decrease in food intake. CGP 71683A has a low affinity for NPY Y(1), Y(2) and Y(4) receptors but a very high affinity for the NPY Y(5) receptor (Ki, 1.4 nM). Surprisingly, CGP 71683A had similarly high affinity for muscarinic receptors (Ki, 2.7 nM) and for the serotonin uptake recognition site (Ki, 6.2 nM) in rat brain. Anatomic analysis of the brain after treatment with CGP 71683A demonstrated an inflammatory response associated with the fall in food intake.

CONCLUSIONS

While the fall in food intake in response to CGP 71683A may have a Y(5) component, interactions with other receptors or inflammatory mediators may also play a role. It is concluded that CGP 71683A is an imprecise tool for investigating the role of the NPY Y(5) receptor in the control of physiological processes including food intake. International Journal of Obesity (2001) 25, 84-94

摘要

引言

本研究的目的是检验以下假设的持续有效性，即大脑中产生的神经肽Y（NPY）通过与NPY Y(5)受体亚型相互作用来控制食物摄入。

方法

使用CGP 71683A对该假设进行检验，CGP 71683A是一种强效且高度选择性的NPY Y(5)受体非肽拮抗剂，将其注入肥胖Zucker fa/fa大鼠的右侧脑室。

结果

在2小时的测试期内，脑室内注射3.4 nmol/kg的NPY可增加食物摄入量。超过15 nmol/kg（脑室内注射）的CGP 71683A剂量可导致NPY引起的食物摄入量增加受到阻断。在黑暗期前每天重复注射CGP 71683A（30 - 300 nmol/kg，脑室内注射）会导致食物摄入量呈剂量依赖性且缓慢发展的减少。CGP 71683A对NPY Y(1)、Y(2)和Y(4)受体的亲和力较低，但对NPY Y(5)受体具有非常高的亲和力（Ki，1.4 nM）。令人惊讶的是，CGP 71683A对大鼠脑中的毒蕈碱受体（Ki，2.7 nM）和5-羟色胺摄取识别位点（Ki，6.2 nM）也具有相似的高亲和力。用CGP 71683A治疗后对大脑进行的解剖分析显示出与食物摄入量下降相关的炎症反应。