Laurino Annunziatina, Landucci Elisa, Raimondi Laura
Section of Pharmacology, Department of Neurology, Psychology, Drug Sciences and Child Health, University of Florence, Florence, Italy.
Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
Front Endocrinol (Lausanne). 2018 Jun 6;9:290. doi: 10.3389/fendo.2018.00290. eCollection 2018.
3-Iodothyronamine (T1AM) is the last iodinated thyronamine generated from thyroid hormone alternative metabolism found circulating in rodents and in humans. So far, the physiopathological meaning of T1AM tissue levels is unknown. Much is instead known on T1AM pharmacological effects in rodents. Such evidence indicates that T1AM acutely modifies, with high potency and effectiveness, rodents' metabolism and behavior, often showing inverted U-shaped dose-response curves. Although several possible targets for T1AM were identified, the mechanism underlying T1AM behavioral effects remains still elusive. T1AM pharmacokinetic features clearly indicate the central nervous system is not a preferential site for T1AM distribution but it is a site where T1AM levels are critically regulated, as it occurs for neuromodulators or neurotransmitters. We here summarize and discuss evidence supporting the hypothesis that central effects of T1AM derive from activation of intracellular and possibly extracellular pathways. In this respect, consisting evidence indicates the intracellular pathway is mediated by the product of T1AM phase-I non-microsomal oxidation, the 3-iodothryoacetic acid, while other data indicate a role for the trace amine-associated receptor, isoform 1, as membrane target of T1AM (extracellular pathway). Overall, these evidence might sustain the non-linear dose-effect curves typically observed when increasing T1AM doses are administered and reveal an interesting and yet unexplored link between thyroid, monoamine oxidases activity and histamine.
3-碘甲腺原氨酸（T1AM）是甲状腺激素替代代谢产生的最后一种碘化甲腺原氨酸，在啮齿动物和人类体内均有发现。到目前为止，T1AM组织水平的生理病理学意义尚不清楚。相反，关于T1AM在啮齿动物中的药理作用却了解很多。这些证据表明，T1AM能高效且有效地急性改变啮齿动物的新陈代谢和行为，剂量-反应曲线通常呈倒U形。尽管已确定了T1AM的几个可能靶点，但其行为效应的潜在机制仍然难以捉摸。T1AM的药代动力学特征清楚地表明，中枢神经系统并非T1AM分布的优先部位，但却是T1AM水平受到严格调控的部位，就像神经调质或神经递质那样。我们在此总结并讨论支持以下假说的证据：T1AM的中枢效应源自细胞内和可能的细胞外途径的激活。在这方面，确凿的证据表明，细胞内途径由T1AM I相非微粒体氧化产物3-碘甲状腺乙酸介导，而其他数据表明，痕量胺相关受体亚型1作为T1AM的膜靶点发挥作用（细胞外途径）。总体而言，这些证据可能支持在给予递增剂量的T1AM时通常观察到的非线性剂量效应曲线，并揭示甲状腺、单胺氧化酶活性和组胺之间一个有趣但尚未探索的联系。
