Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Hungary; Molecular Pharmacology Research Group, János Szentágothai Research Centre, Centre for Neuroscience, University of Pécs, Hungary.
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Hungary; Molecular Pharmacology Research Group, János Szentágothai Research Centre, Centre for Neuroscience, University of Pécs, Hungary; MTA-PTE NAP B Chronic Pain Research Group, Hungary.
Neuropeptides. 2017 Aug;64:9-17. doi: 10.1016/j.npep.2016.12.003. Epub 2016 Dec 13.
Hemokinin-1 (HK-1), the newest tachykinin encoded by the Tac4 gene was discovered in 2000. Its name differs from that of the other members of this peptide family due to its first demonstration in B lymphocytes. Since tachykinins are classically found in the nervous system, the significant expression of HK-1 in blood cells is a unique feature of this peptide. Due to its widespread distribution in the whole body, HK-1 is involved in different physiological and pathophysiological functions involving pain inflammation modulation, immune regulation, respiratory and endocrine functions, as well as tumor genesis. Furthermore, despite the great structural and immunological similarities to substance P (SP), the functions of HK-1 are often different or the opposite. They both have the highest affinity to the tachykinin NK1 receptor, but HK-1 is likely to have a distinct binding site and signalling pathways. Moreover, several actions of HK-1 different from SP have been suggested to be mediated via a presently not identified own receptor/target molecule. Therefore, it is very important to explore its effects at different levels and compare its characteristics with SP to get a deeper insight in the different cellular mechanisms. Since HK-1 has recently been in the focus of intensive research, in the present review we summarize the few clinical data and experimental results regarding HK-1 expression and function in different model systems obtained throughout the 16years of its history. Synthesizing these findings help to understand the complexity of HK-1 actions and determine its biomarker values and/or drug development potentials.
血激肽-1（HK-1）是 2000 年发现的 Tac4 基因编码的最新速激肽。由于它首先在 B 淋巴细胞中被发现，因此其名称与该肽家族的其他成员不同。由于速激肽通常存在于神经系统中，因此 HK-1 在血细胞中的大量表达是该肽的一个独特特征。由于其在全身的广泛分布，HK-1 参与了不同的生理和病理生理功能，包括疼痛炎症调节、免疫调节、呼吸和内分泌功能以及肿瘤发生。此外，尽管与 P 物质（SP）具有很大的结构和免疫相似性，但 HK-1 的功能往往不同或相反。它们都与速激肽 NK1 受体具有最高的亲和力，但 HK-1 可能具有独特的结合位点和信号通路。此外，已经提出了 HK-1 的几种不同于 SP 的作用是通过目前尚未确定的自身受体/靶分子介导的。因此，探索其在不同水平上的作用并将其特性与 SP 进行比较，以深入了解不同的细胞机制非常重要。由于 HK-1 最近成为研究的焦点，在本综述中，我们总结了在其历史的 16 年中，在不同模型系统中关于 HK-1 表达和功能的一些临床数据和实验结果。综合这些发现有助于理解 HK-1 作用的复杂性，并确定其生物标志物价值和/或药物开发潜力。
