摘要
Prokineticin 1和prokineticin 2属于一个新的趋化因子科,在包括哺乳动物在内的几个物种中鉴定,其特征是存在五种二硫键。 这些蛋白通过两个G-偶联受体(prokineticin-Receptor 1和prokineticin-receptor 2)发出信号,它们在所有组织中广泛表达,并参与大量的生物活动。包括血管生成、造血、免疫过程、炎症和伤害性传递。Prokineticin 2在炎症组织中过表达,在中性粒细胞依赖的infl中起重要作用。子弹和超痛觉。 随着组织炎症、周围神经损伤、肿瘤、骨转移,运动素2和前列腺素受体2在背根神经节和脊柱内的表达也增加。拉索。Prokineticin受体在痛觉感受器末端和背根神经节中高表达,对TRPV 1和TRPA 1有促进作用,促进外周敏化。Prokineticin 2-induCES激活脊髓背角和活化星形胶质细胞内的Prokineticin受体可促进中枢敏化,维持慢性和神经性疼痛。 Prokineticin 2作用于单核细胞、巨噬细胞和树突状细胞上的prokineticin受体,诱导趋化作用,释放炎症细胞因子和原感受器细胞因子。因此,Prokineticin系统EM是治疗慢性疼痛的新靶点。对丙激肽2的作用机理及其抑制作用的潜在效果进行了探讨。
关键词: Prokineticin系统,慢性疼痛,炎症,G-偶联受体,趋化因子,Prok系统。
Current Medicinal Chemistry
Title:Targeting the Prokineticin System to Control Chronic Pain and Inflammation
Volume: 25 Issue: 32
关键词: Prokineticin系统,慢性疼痛,炎症,G-偶联受体,趋化因子,Prok系统。
摘要: Prokineticin1 and prokineticin2 belong to a new family of chemokines identified in several species including mammals and characterized by the presence of five disulfide bridges.
These proteins signal through two G-coupled receptors (prokineticin-receptor1 and prokineticin- receptor2) widely expressed in all tissues and involved in a large spectrum of biological activities, including angiogenesis, hematopoiesis, immune processes, inflammation and nociceptive transmission. Prokineticin2 is overexpressed in inflamed tissues and has a crucial role in neutrophil dependent inflammation and hypernociception.
Following tissue inflammation, peripheral nerve injury, cancer, bone metastasis the expression of prokineticin2 and of the prokineticin-receptor2 is increased also within dorsal root ganglia and spinal cord. Prokineticin receptors, highly expressed in nociceptor endings and dorsal root ganglia, exert a tonic activation of TRPV1 and TRPA1 contributing to peripheral sensitization. Prokineticin2-induces activation of the prokineticin receptors in the spinal dorsal horn and in activated astrocytes contributes to central sensitization and maintains chronic and neuropathic pain.
Prokineticin2, acting on prokineticin receptors on monocytes, macrophages and dendritic cells, induces chemotaxis and release of inflammatory and pronociceptive cytokines. Hence, the prokineticin system represents a novel therapeutic target in chronic pain conditions. Evaluation of the mechanism of action of prokineticin2 and the potential effectiveness of its inhibition is discussed.
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Targeting the Prokineticin System to Control Chronic Pain and Inflammation, Current Medicinal Chemistry 2018; 25 (32) . https://dx.doi.org/10.2174/0929867324666170713102514
DOI https://dx.doi.org/10.2174/0929867324666170713102514 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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