Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD, USA.
Front Endocrinol (Lausanne). 2012 Oct 9;3:120. doi: 10.3389/fendo.2012.00120. eCollection 2012.
Taltirelin (TAL) is a thyrotropin-releasing hormone (TRH) analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R) in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating central nervous system effects in humans compared to TRH.
他利瑞林（TAL）是一种促甲状腺素释放激素（TRH）类似物，在日本被批准用于人体。在这项研究中，我们在模型细胞系统中对 TAL 与人促甲状腺素受体（TRH-R）的结合和信号转导进行了表征。我们发现，与 TRH 相比，TAL 表现出较低的结合亲和力和较低的通过三磷酸肌醇/钙途径的信号转导效力。然而，TAL 刺激三磷酸肌醇第二信使生成的内在效力比 TRH 更高。这是首次阐明 TAL 在 TRH-R 上的药理学特性的研究，并表明 TAL 是 TRH-R 的超激动剂。我们认为，TAL 表现出的超激动作用可能部分解释了它在介导人类中枢神经系统效应方面比 TRH 具有更高的活性。
