Substance P(Neurokinin P,AbMole,M9080)是一种11氨基酸的神经肽,属于速激肽家族,主要通过激活神经激肽1受体(NK1R)介导信号传导,涉及痛觉传递、炎症调节和细胞间通信等细胞活动,还能调节钙离子流量、ERK磷酸化和NF-κB活化等过程[1]。在细胞实验方面,Substance P(CAS No.:33507-63-0)在H9C2大鼠心肌细胞中以1-10 nM浓度预处理后,可增加细胞中磷酸化Akt(p-Akt)的水平并抑制缺氧/再氧合诱导的细胞凋亡[2];Substance P在皮肤肥大细胞中,可诱导浓度依赖性的组胺释放,而阻断NK1R后可抑制此效应[3];Substance P还在SiHa宫颈癌细胞中,以浓度依赖方式促进增殖和侵袭,并激活ERK1/2磷酸化[4];Substance P在兔成骨细胞模型中,以1 μM的浓度有效促进成骨分化和组织修复[5];Substance P(Neurokinin P)还可以用于神经系统和疼痛相关的研究,例如在ICR小鼠神经性疼痛模型中的研究显示,静脉注射Neurokinin P(1 nmol/kg)可抑制疼痛相关炎症和疼痛因子的活性[6];Substance P在豚鼠和人类迷走神经中,引起去极化,而Aprepitant 可抑制上述效应[7];Substance P还在猪急性心肌梗塞模型中,通过静脉注射(5 nmol/kg)后提供心脏保护作用[8]。上述这些研究揭示了Substance P在细胞信号传导和动物模型中的多功能性,为理解其生物学作用提供了基础。
参考文献及鸣谢
1\] Spitsin, S.; Pappa, V.; Douglas, S. D. Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling. *Journal of leukocyte biology* **2018**. \[2\] Xu, Y.; Gu, Q.; Tang, J.; et al. Substance P Attenuates Hypoxia/Reoxygenation-Induced Apoptosis via the Akt Signalling Pathway and the NK1-Receptor in H9C2Cells. *Heart, lung \& circulation* **2018** , *27* (12), 1498-1506. \[3\] Hermans, M. A. W.; Schrijver, B.; van Holten-Neelen, C.; et al. The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release. *Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology* **2018** , *48* (11), 1412-1420. \[4\] Wang, Y.; Yuan, S.; Ma, J.; et al. Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells \in vitro\. *European journal of histochemistry : EJH* **2023** , *67* (3). \[5\] Chen, J.; Liu, W.; Zhao, J.; et al. Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in osteoporotic rabbits. *Biotechnology letters* **2017** , *39* (3), 465-472. \[6\] Chung, E.; Yoon, T. G.; Kim, S.; et al. Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors. *Biomolecules \& therapeutics* **2017** , *25* (3), 259-265. \[7\] Smith, J. A.; Harle, A.; Dockry, R.; et al. Aprepitant for Cough in Lung Cancer. A Randomized Placebo-controlled Trial and Mechanistic Insights. *American journal of respiratory and critical care medicine* **2021** , *203* (6), 737-745. \[8\] Sim, D. S.; Kim, W.; Lee, K. H.; et al. Cardioprotective effect of substance P in a porcine model of acute myocardial infarction. *International journal of cardiology* **2018** , *271*, 228-232.