Chaffer Christine L, Morris Margaret J
Department of Pharmacology, University of Melbourne, Melbourne, Victoria 3010, Australia.
Endocrinology. 2002 Jan;143(1):191-7. doi: 10.1210/endo.143.1.8569.
Melanin-concentrating hormone (MCH) and NPY are orexigenic peptides localized in the lateral hypothalamic area and arcuate nucleus, respectively. Although both NPY- and MCH-containing fibers innervate areas of the hypothalamus implicated in feeding, the extent to which the regulation of appetite is dependent on interactions between these peptides is unknown. Daytime feeding responses to 2 nmol MCH, 1 nmol NPY, or vehicle were investigated in male Sprague Dawley rats previously implanted with intracerebroventricular cannulas. The effects of prior administration of the Y(1)-receptor antagonists BIBO 3304 (20 nmol) or GR231118 (5 nmol) on these responses were examined. NPY and MCH stimulated food intake relative to vehicle (4 h intake, 5.9 +/- 0.7 and 3.6 +/- 0.2 g, respectively; P < 0.0001). BIBO 3304 and GR231118 significantly inhibited MCH- induced feeding by 73% (P < 0.01) and 86% (P < 0.01), respectively, at 2 h. Coadministration of NPY and MCH did not increase food intake above that in response to NPY alone; however, prior administration of BIBO 3304 resulted in a less marked inhibition of feeding (P < 0.05, 30 min only). Inhibition of MCH-induced feeding by two structurally different NPY Y(1)-receptor antagonists provides strong evidence that the orexigenic action of MCH involves the Y(1)-receptor.
黑色素浓缩激素（MCH）和神经肽Y（NPY）是分别位于下丘脑外侧区和弓状核的促食欲肽。尽管含NPY和MCH的纤维均支配与进食有关的下丘脑区域，但食欲调节在多大程度上依赖于这些肽之间的相互作用尚不清楚。在先前已植入脑室内插管的雄性Sprague Dawley大鼠中，研究了它们对2 nmol MCH、1 nmol NPY或赋形剂的日间进食反应。研究了预先给予Y（1）受体拮抗剂BIBO 3304（20 nmol）或GR231118（5 nmol）对这些反应的影响。相对于赋形剂，NPY和MCH刺激了食物摄入（4小时摄入量分别为5.9±0.7克和3.6±0.2克；P<0.0001）。BIBO 3304和GR231118在2小时时分别显著抑制MCH诱导的进食达73%（P<0.01）和86%（P<0.01）。NPY和MCH共同给药并未使食物摄入量增加超过单独给予NPY时的摄入量；然而，预先给予BIBO 3304导致进食抑制作用不太明显（仅在30分钟时P<0.05）。两种结构不同的NPY Y（1）受体拮抗剂对MCH诱导的进食的抑制作用提供了有力证据，表明MCH的促食欲作用涉及Y（1）受体。
