Autoradiographic analysis of ghrelin receptors in the rat hypothalamus
Autoradiographic analysis of ghrelin receptors in the rat hypothalamus
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DOI：
10.1016/j.brainres.2007.12.055
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发表时间：
2008-02-27
期刊：
影响因子：
2.9
通讯作者：
Pinkney, Jonathon
中科院分区：
文献类型：
--
作者：
Harrold, Joanne A.;Dovey, Terence;Pinkney, Jonathon
Ghrelin对食物摄入有强烈的刺激作用。据推测，它通过结合生长激素促分泌素受体（GHS-R）来增加摄食，GHS-R是迄今为止确定的这种胃激素的唯一作用部位。最初，生长激素释放肽结合位点的分布只能从GHS-R mRNA的表达模式或使用免疫组织化学技术来检查c-fos表达来确定。然而，一种新的放射性配体（[I-125-his（9）]-ghrelin）的表征使得GHS-R受体蛋白的分布能够被直接证明。在这里，使用定量放射自显影，我们调查的分布和密度的饥饿素受体在啮齿动物下丘脑。在调节食欲的弓状核、下丘脑腹内侧核、室旁核、背内侧核和丘脑腹外侧核中发现了特异性结合。下丘脑核和下丘脑外侧区的GHS-R mRNA的分布模式相对应。令人惊讶的是，在营养状态改变后，在这些结合位点中的任何一个中都没有发现受体密度的变化，尽管发现了血浆生长素释放肽水平的相关改变。我们认为，这可能涉及到的范例，用于修改营养状况的研究，或可能表明，外周生长激素释放肽是不太可能的主要来源的生长激素释放肽，在许多下丘脑网站的行为。(C)2007 Elsevier B. V.保留所有权利。
Ghrelin exerts potent stimulatory effects on food intake. It is assumed to increase feeding by binding at growth hormone secretagogue receptors (GHS-R), the only sites of action for this gastric hormone identified to date. Initially, the distribution of ghrelin binding sites could only be determined from expression patterns of GHS-R mRNA or the use of immunohistochemical techniques to examine c-fos expression. However, the characterisation of a novel radioligand ([I-125-his(9)]-ghrelin), has enabled the distribution of GHS-R receptor protein to be directly demonstrated. Here, using quantitative autoradiography, we investigate the distribution and density of ghrelin receptors in the rodent hypothalamus. Specific binding was identified in the appetite-regulating arcuate nucleus, ventromedial hypothalamic nucleus, paraventricular nucleus, dorsomedial. hypothalamic nucleus and the lateral hypothalamic area corresponding to the previously reported distribution pattern of GHS-R mRNA. Surprisingly, variations in receptor density were not identified in any of these binding sites upon a change in nutritional status, despite relevant alterations in plasma ghrelin levels being identified. We suggest that this may relate to the paradigm employed to modify nutritional status in the study or could indicate that peripheral ghrelin is unlikely to be the major source of ghrelin that acts in many hypothalamic sites. (C) 2007 Elsevier B.V. All rights reserved.