Substance P, an important neuropeptide neurotransmitter, stimulates phosphatidylinositol turnover with an EC50 value of 0.36nM[1]. Substance P has been widely used in the research of pain regulation, emotion regulation and bone metabolism regulation[2-3].
In vitro, Substance P (10nM) treatment induced Akt phosphorylation at Ser-473 in a time-dependent manner and persisted over the 60-minute incubation period in colonic epithelial NCM460 colonocytes[4]. Treatment with 10nM Substance P for 8 hours inhibited tamoxifen (10μM; 8h) induced cell death of NCM460 colonocytes, and cell proliferation was stimulated by treatment with 10nM Substance P for 8h in the absence of tamoxifen[4]. Treatment of buffalo fetal fibroblasts (10nM) with Substance P alone resulted in significant cell proliferation and migration in both horizontal and vertical directions within 24 hours[5].
In vivo, topical application of Substance P (32μg/day per wound dissolved in saline) for 10 days improved wound healing and reduced wound size in a diabetic mouse model[6]. A single dose of topical Substance P treatment (0.5μg/wound) promoted wound closure and epithelial regeneration within 14 days, thereby enhancing wound healing in a skin full-thickness wound model of mouse[7].
References:
[1] Torrens Y, Beaujouan J C, Saffroy M, et al. Substance P receptors in primary cultures of cortical astrocytes from the mouse[J]. Proceedings of the National Academy of Sciences, 1986, 83(23): 9216-9220.
[2] Li F X Z, Xu F, Lin X, et al. The role of substance P in the regulation of bone and cartilage metabolic activity[J]. Frontiers in Endocrinology, 2020, 11: 77.
[3] Humes C, Sic A, Knezevic N N. Substance P’s impact on chronic pain and psychiatric conditions—a narrative review[J]. International journal of molecular sciences, 2024, 25(11): 5905.
[4] Koon H W, Zhao D, Zhan Y, et al. Substance P mediates antiapoptotic responses in human colonocytes by Akt activation[J]. Proceedings of the National Academy of Sciences, 2007, 104(6): 2013-2018.
[5] Kant V, Mahapatra P S, Gupta V, et al. Substance P, a neuropeptide, promotes wound healing via neurokinin-1 receptor[J]. The International Journal of Lower Extremity Wounds, 2023, 22(2): 291-297.
[6] Leal E C, Carvalho E, Tellechea A, et al. Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype[J]. The American journal of pathology, 2015, 185(6): 1638-1648.
[7] Kumar S, Tan Y, Berthiaume F. Neuropeptide substance p enhances skin wound healing in vitro and in vivo under hypoxia[J]. Biomedicines, 2021, 9(2): 222.
Substance P作为一种重要的神经肽类神经递质，能够刺激磷脂酰肌醇代谢，EC50值为0.36nM[1]。Substance P已被广泛应用于疼痛调节、情绪调控及骨代谢研究领域[2-3]。
在体内，10nM浓度的Substance P处理可诱导结肠上皮NCM460细胞中Akt蛋白Ser-473位点的磷酸化，且这种磷酸化作用呈时间依赖性，在60分钟孵育期内持续存在[4]。使用10nM浓度的Substance P处理8小时能抑制他莫昔芬（10μM；8小时）诱导的NCM460细胞死亡，而在无他莫昔芬条件下，10nM 浓度的Substance P处理8小时刺激细胞增殖[4]。单独使用10nM浓度的Substance P处理水牛胎儿成纤维细胞24小时，可显著促进细胞在水平和垂直方向上的增殖与迁移[5]。
在体外，局部施用Substance P（32μg/day/伤口，溶于生理盐水）连续10天能改善糖尿病小鼠模型的伤口愈合并缩小创面面积[6]。单次局部施用Substance P（0.5μg/伤口）治疗可在14天内促进小鼠皮肤全层缺损模型的伤口闭合和上皮再生，从而加速创面愈合[7]。