Research Center "E. Piaggio", Faculty of Engineering, University of Pisa, Via Diotisalvi 2, 56126, Pisa, PI, Italy,
Cell Biochem Biophys. 2014 Jan;68(1):37-47. doi: 10.1007/s12013-013-9680-y.
3-Iodothyronamine (T1AM) is regarded as a hormone-like substance thanks to its endogenous nature, its interaction with specific receptors trace amine-associated receptor 1 and its biological effects. We characterized T1AM transport and conversion in an in vitro culture of H9c2 murine cells, after a T1AM bolus injection. Samples of cell medium culture and cell lysate were assayed by high-performance liquid chromatography coupled to tandem mass spectrometry. We performed comparative experiments by adding to T1AM bolus amino oxidase inhibitors as iproniazid, pargyline (monoamine oxidase, MAO inhibitors), aminoguanidine, and semicarbazide (semicarbazide-sensitive amino oxidase, SSAO inhibitors). A mathematical model was developed, based on the assumption that T1AM is transported with a mechanism that is typical of hormone transport (i.e., EGF or insulin). We noticed that surface receptors downregulation could play a major role in T1AM dynamics. We also estimated that T1AM catabolism is mainly affected by MAO inhibitors, which produce a dramatic decrease in the kinetic constants related to T1AM degradation, while no significant changes were observed in experiments with SSAO inhibitors.
3-碘甲状腺原氨酸（T1AM）因其内源性、与特定受体——痕量胺相关受体 1（trace amine-associated receptor 1）相互作用以及生物学效应，被视为一种类激素物质。我们在 H9c2 鼠细胞的体外培养物中对 T1AM 脉冲注射后的 T1AM 转运和转化进行了研究。通过高效液相色谱-串联质谱法对细胞培养液和细胞裂解物样本进行了检测。我们通过添加氨基酸氧化酶抑制剂（异丙烟肼、帕吉林[单胺氧化酶，MAO 抑制剂]、氨基胍和氨基硫脲[氨基硫脲敏感的氨基酸氧化酶，SSAO 抑制剂]进行了对比实验。我们基于 T1AM 是通过与表皮生长因子（EGF）或胰岛素类似的激素转运机制进行转运的假设，建立了一个数学模型。我们注意到，表面受体下调可能在 T1AM 动力学中发挥主要作用。我们还估计，MAO 抑制剂主要影响 T1AM 的代谢，这会导致与 T1AM 降解相关的动力学常数显著下降，而在 SSAO 抑制剂实验中则没有观察到明显变化。
