Trace amine-associated receptors (TAAR) as targets for thyronamines

3-碘甲状腺原氨酸（T1 AM）是甲状腺激素的内源性衍生物和降解产物，具有多种生物学功能，如降低体温、心率和代谢，并且是痕量胺相关受体1（TAAR 1）的激动剂。TAAR 1首先作为受体被微量胺激活，即β-苯乙胺，p-酪胺和色胺，但也被精神活性化合物如MDMA，安非他明和LSD激活。TAAR 1是Gαs蛋白偶联受体，是TAAR家族的成员，在哺乳动物中由9种亚型组成。在这里，我们测试的假设，整个TAAR家族可能被激活的甲状腺激素的代谢产物。具体而言，T1 AM行动在所有TAAR家族成员，T1 AM功能在TAAR 1的进化保守性，配体特异性的分子基础和TAAR冗余的功能相关性将被研究。此外，一个排他性的细胞内（不质膜结合）信号传导以及非G蛋白介导的T1 AM信号传导的概念将具体解决。作为这项研究的结果，我们将从根本上扩大我们的知识的分子机制和T1 AM行动的后果。

3-iodothyronamine (T1AM), an endogenous derivative and degradation product of thyroid hormones, exerts several biological functions, like reduction of body temperature, heart rate, and metabolism, and is an agonist at trace amine-associated receptor 1 (TAAR1). TAAR1 was first deorphanized as receptor activated by trace amines, namely β-phenylethylamine, p-tyramine and tryptamine, but also by psychoactive compounds like MDMA, amphetamine and LSD. TAAR1 is a Gαs protein-coupled receptor and a member of the TAAR family consisting of nine subtypes in mammals. Here we test the hypothesis that the entire TAAR family may be activated by metabolites of thyroid hormones. Specifically, T1AM action at all TAAR family members, the evolutionary conservation of T1AM function at TAAR1, the molecular basis of ligand specificity and the functional relevance of TAAR redundancy will be studied. Further, the concept of an exclusive intracellular (not plasma membrane bound) signalling as well as non-G protein-mediated signalling of T1AM will be specifically addressed. As an outcome of this study we will fundamentally extent our knowledge of the molecular mechanisms and consequences of T1AM action.