The Human Bitter Taste Receptor hTAS2R50 Is Activated by the Two Natural Bitter Terpenoids Andrographolide and Amarogentin
The Human Bitter Taste Receptor hTAS2R50 Is Activated by the Two Natural Bitter Terpenoids Andrographolide and Amarogentin
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DOI：
10.1021/jf9014334
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发表时间：
2009-11-11
影响因子：
6.1
通讯作者：
Meyerhof, Wolfgang
中科院分区：
文献类型：
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作者：
Behrens, Maik;Brockhoff, Anne;Meyerhof, Wolfgang
哺乳动物的苦味感知是通过激活位于口腔中的专用苦味受体来介导的。基因组分析揭示了直口哺乳动物苦味受体基因的存在，这些基因可能识别不同物种中的相同化合物，以及被认为在进化过程中发挥关键作用的物种特异性受体基因扩增。在人类中，25种苦味受体中的8种（hTAS 2 Rs）是这种扩展的受体基因亚家族的密切相关成员。这项研究确定了两种天然苦味萜类化合物，穿心莲内酯和苦杏仁苷，这是孤儿受体hTAS2R50的激动剂，最远的成员的亚家族。本文介绍了该受体的药理学特性，并分析了其与先前去孤儿hTAS2R43，hTAS2R44，hTAS2R46和hTAS2R47的功能关系。深入了解一般宽度的调整，功能冗余，药理学激活模式和氨基酸同源性，这个受体亚家族之间的关系。
Bitterness perception in mammals is mediated through activation of dedicated bitter taste receptors located in the oral cavity. Genomic analyses revealed the existence of orthologous mammalian bitter taste receptor genes, which presumably recognize the same compounds in different species, as well as species-specific receptor gene expansions believed to fulfill a critical role during evolution. In man, 8 of the 25 bitter taste receptors (hTAS2Rs) are closely related members of such an expanded subfamily of receptor genes. This study identified two natural bitter terpenoids, andrographolide and amarogentin, that are agonists for the orphan receptor hTAS2R50, the most distant member of the subfamily. This paper presents the pharmacological characterization of this receptor and analyzes its functional relationship with the previously deorphaned hTAS2R43, hTAS2R44, hTAS2R46, and hTAS2R47. Insights into the general breadth of tuning, functional redundancies, and relationships between pharmacological activation patterns and amino acid homologies for this receptor subfamily are presented.