Thirty-seven years of MT1 and MT2 melatonin receptor localization in the brain: Past and future challenges

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Paul Klosen
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Abstract

Identifying the target cells of a hormone is a key step in understanding its function. Once the molecular nature of the receptors for a hormone has been established, researchers can use several techniques to detect these receptors. Here I will review the different tools used over the years to localize melatonin receptors and the problems associated with each of these techniques. The radioligand 2-[125I] iodomelatonin was the first tool to allow localization of melatonin receptors on tissue sections. Once the MT1 and MT2 receptors were cloned, in situ hybridization could be used to detect the messenger RNA for these receptors. The deduced amino acid sequences for MT1 and MT2 receptors allowed the production of peptide immunogens to generate antibodies against the MT1 and MT2 receptors. Finally, transgenic reporters driven by the promoter elements of the MT1 and MT2 genes have been used to map the expression of MT1 and MT2 in the brain and the retina. Several issues have complicated the localization of melatonin receptors and the characterization of melatonin target cells over the last three decades. Melatonin receptors are expressed at low levels, leading to sensitivity issues for their detection. The second problem are specificity issues with antibodies directed against the MT1 and MT2 melatonin receptors. These receptors are G protein-coupled receptors and many antibodies directed against such receptors have been shown to present similar problems concerning their specificity. Despite these specificity problems which start to be seriously addressed by recent studies, antibodies will be important tools in the future to identify and phenotype melatonin target cells. However, we will have to be more stringent than previously when establishing their specificity. The results obtained by these antibodies will have to be confronted and be coherent with results obtained by other techniques.

Abstract Image

脑内 MT1 和 MT2 褪黑激素受体定位 37 年:过去和未来的挑战
确定激素的靶细胞是了解其功能的关键一步。一旦确定了激素受体的分子性质,研究人员就可以使用多种技术来检测这些受体。在此,我将回顾多年来用于定位褪黑激素受体的不同工具,以及与每种技术相关的问题。放射性配体 2-[125I]碘褪黑激素是第一种在组织切片上定位褪黑激素受体的工具。一旦克隆出 MT1 和 MT2 受体,就可以使用原位杂交技术检测这些受体的信使 RNA。推导出 MT1 和 MT2 受体的氨基酸序列后,就可以生产多肽免疫原,产生针对 MT1 和 MT2 受体的抗体。最后,由 MT1 和 MT2 基因启动子元件驱动的转基因报告基因被用来绘制 MT1 和 MT2 在大脑和视网膜中的表达图。过去三十年来,有几个问题使褪黑激素受体的定位和褪黑激素靶细胞的特征描述变得复杂。褪黑激素受体的表达水平较低,导致检测灵敏度问题。第二个问题是针对 MT1 和 MT2 褪黑激素受体的抗体的特异性问题。这些受体是 G 蛋白偶联受体,许多针对此类受体的抗体都存在类似的特异性问题。尽管最近的研究开始认真解决这些特异性问题,但抗体仍将是未来识别褪黑激素靶细胞并对其进行表型的重要工具。不过,在确定其特异性时,我们必须比以前更加严格。这些抗体获得的结果必须与其他技术获得的结果相一致。
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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