Kinin receptors in pain and inflammation
Kinin receptors in pain and inflammation
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DOI：
10.1016/s0014-2999(01)01318-8
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发表时间：
2001-10-19
影响因子：
5
通讯作者：
Cloutier, F
中科院分区：
文献类型：
--
作者：
Couture, R;Harrisson, M;Cloutier, F
激肽是参与炎症、血管和疼痛过程的最有效的自泌素之一。这些短寿命的肽，包括缓激肽、激肽和T-激肽，在组织损伤和伤害性刺激过程中产生。然而，新出现的证据也表明，激肽储存在中枢神经系统（CNS）的神经元元件中，它们被认为在各种脑功能中，特别是在控制伤害性信息中发挥神经介质的作用。激肽通过激活两个跨膜G蛋白偶联受体发挥其生物学作用，所述受体被称为缓激肽B-1和B-2。尽管B-2受体是组成型的并被母体分子激活，但B-1受体通常在正常组织中表达不足，并被剥夺C-末端Arg的激肽（des-Arg（9）-激肽）激活。B-1受体的诱导和表达增加发生在组织损伤后或用细菌内毒素或细胞因子如白细胞介素-1 β和肿瘤坏死因子-α治疗后。这篇综述总结了最近的数据，从各种动物模型传达支持的作用，B-2受体在急性期的炎症和疼痛反应，和B-1受体的作用，在慢性期的反应。B-1受体可能在具有免疫成分的炎性疾病（糖尿病、哮喘、类风湿性关节炎和多发性硬化症）中发挥战略作用。提供了新的信息有关的作用，感觉机制subserving脊髓痛觉过敏和胸膜内中性粒细胞迁移发生后，B-1受体激活的链脲佐菌素治疗的大鼠，胰岛素依赖性糖尿病的模型，其中B-1受体似乎是迅速过表达。尽管广泛接受用特异性拮抗剂阻断激肽受体可有益于治疗躯体和内脏炎症和疼痛，最近的分子和功能证据表明，用激动剂激活B-1受体可能通过减少免疫细胞浸润而为多发性硬化症中遇到的CNS炎性脱髓鞘疾病提供新的治疗方法（T淋巴细胞）进入大脑。因此，B-1受体可根据炎性疾病发挥保护或有害作用。B-1受体的这种双重功能值得进一步研究。(C)2001 Elsevier Science B. V.保留所有权利。
Kinins are among the most potent autacoids involved in inflammatory, vascular and pain processes. These short-lived peptides, including bradykinin, kallidin and T-kinin, are generated during tissue injury and noxious stimulation. However, emerging evidence also suggests that kinins are stored in neuronal elements of the central nervous system (CNS) where they are thought to play a role as neuromediators in various cerebral functions, particularly in the control of nociceptive information. Kinins exert their biological effects through the activation of two transmembrane G-protein-coupled receptors, denoted bradykinin B-1 and B-2 Whereas the B-2 receptor is constitutive and activated by the parent molecules, the B-1 receptor is generally underexpressed in normal tissues and is activated by kinins deprived of the C-terminal Arg (des-Arg(9)-kinins). The induction and increased expression of B-1 receptor occur following tissue injury or after treatment with bacterial endotoxins or cytokines such as interleukin-1beta and tumor necrosis factor-alpha. This review summarizes the most recent data from various animal models which convey support for a role of B-2 receptors in the acute phase of the inflammatory and pain response, and for a role of B-1 receptors in the chronic phase of the response. The B-1 receptor may exert a strategic role in inflammatory diseases with an immune component (diabetes, asthma, rheumatoid arthritis and multiple sclerosis). New information is provided regarding the role of sensory mechanisms subserving spinal hyperalgesia and intrapleural neutrophil migration that occur upon B-1 receptor activation in streptozotocin-treated rats, a model of insulin-dependent diabetes mellitus in which the B-1 receptor seems to be rapidly overexpressed. Although it is widely accepted that the blockade of kinin receptors with specific antagonists could be of benefit in the treatment of somatic and visceral inflammation and pain, recent molecular and functional evidence suggests that the activation of B-1 receptors with an agonist may afford a novel therapeutic approach in the CNS inflammatory demyelinating disorder encountered in multiple sclerosis by reducing immune cell infiltration (T-lymphocytes) into the brain. Hence, the B-1 receptor may exert either a protective or detrimental effect depending on the inflammatory disease. This dual function of the B-1 receptor deserves to be investigated further. (C) 2001 Elsevier Science B.V. All rights reserved.