Parrado C, Díaz-Cabiale Z, García-Coronel M, Agnati L F, Coveñas R, Fuxe K, Narváez J A
Department of Histology, University of Málaga, Faculty of Medicine, Campus de Teatinos s/n, Malaga 29080, Spain.
Neuropharmacology. 2007 Feb;52(2):684-92. doi: 10.1016/j.neuropharm.2006.09.010. Epub 2006 Nov 7.
The aim of this work was to determine the interactions between NPY and GAL receptor (GALR) subtypes in the hypothalamus and the amygdala using quantitative receptor autoradiography to analyze the binding characteristics of NPY-Y1 and Y2 receptor subtypes in the presence and absence of GAL. Food intake in satiated animals was evaluated after intraventricular co-injections of GAL and NPY-Y1 or Y2 agonists. The expression of c-Fos IR in both regions was also investigated. GAL decreases NPY-Y1 agonist binding in the arcuate nucleus by about 15% (p<0.01), but increases NPY-Y1 agonist binding in amygdala (18%) (p<0.01). These effects were blocked with the GAL antagonist M35. Y2-agonist binding was not modified by GAL. GAL blocked the food intake induced by the Y1 agonist (p<0.01). Co-injections of Y1 agonist and GAL also reduced the c-Fos expression induced by the Y1 agonist in the arcuate nucleus and the dorsomedial hypothalamic nucleus but increased c-Fos expression in amygdala. These results indicate the existence of antagonistic interactions between GALR and NPY-Y1 receptors in the hypothalamus and their functional relevance for food intake. In contrast, a facilitatory interaction between GALR and Y1 receptors exists in the amygdala which may be of relevance for fear related behaviour.
本研究旨在利用定量受体放射自显影技术,分析下丘脑和杏仁核中神经肽Y(NPY)与甘丙肽受体(GALR)亚型之间的相互作用,以研究在有或无甘丙肽(GAL)存在的情况下NPY - Y1和Y2受体亚型的结合特性。对饱足动物进行脑室内共注射GAL与NPY - Y1或Y2激动剂后,评估其食物摄入量。同时还研究了这两个区域中c-Fos免疫反应(IR)的表达。GAL使弓状核中NPY - Y1激动剂的结合减少约15%(p<0.01),但使杏仁核中NPY - Y1激动剂的结合增加(18%)(p<0.01)。这些作用可被GAL拮抗剂M35阻断。Y2激动剂的结合不受GAL影响。GAL可阻断Y1激动剂诱导的食物摄入(p<0.01)。Y1激动剂与GAL的共注射还降低了弓状核和下丘脑背内侧核中Y1激动剂诱导的c-Fos表达,但增加了杏仁核中的c-Fos表达。这些结果表明下丘脑内GALR与NPY - Y1受体之间存在拮抗相互作用,且它们在食物摄入方面具有功能相关性。相反,杏仁核中GALR与Y1受体之间存在促进性相互作用,这可能与恐惧相关行为有关。