Walker K, Perkins M, Dray A
Sandoz Institute for Medical Research, London, U.K.
Neurochem Int. 1995 Jan;26(1):1-16; discussion 17-26. doi: 10.1016/0197-0186(94)00114-a.
Kinins, including bradykinin and kallidin, are peptides that are produced and act at the site of tissue injury or inflammation. They induce a variety of effects via the activation of specific B1 or B2 receptors that are coupled to a number of biochemical transduction mechanisms. In the periphery the actions of kinins include vasodilatation, increased vascular permeability and the stimulation of immune cells and peptide-containing sensory neurones to induce pain and a number of neuropeptide-induced reflexes. Mechanisms for kinin synthesis are also present in the CNS where kinins are likely to initiate a similar cascade of events, including an increase in blood flow and plasma leakage. Kinins are potent stimulators of neural and neuroglial tissues to induce the synthesis and release of other pro-inflammatory mediators such as prostanoids and cytotoxins (cytokines, free radicals, nitric oxide). These events lead to neural tissue damage as well as long lasting disturbances in blood-brain barrier function. Animal models for CNS trauma and ischaemia show that increases in kinin activity can be reversed either by kinin receptor antagonists or by the inhibition of kinin production. A number of other central actions have been attributed to kinins including an effect on pain signalling, both within the brain (which may be related to vascular headache) and within the spinal dorsal horn where primary afferent nociceptors can be stimulated. Kinins also appear to play a role in cardiovascular regulation especially during chronic spontaneous hypertension. Presently, however, direct evidence is lacking for the release of kinins in pathophysiological conditions of the CNS and it is not known whether spinal or central neurones, other than afferent nerve terminals, are sensitive to kinins. A more detailed examination of the effects of kinins and their central pharmacology is necessary. It is also important to determine whether the inhibition of kinin activity will alleviate CNS inflammation and whether kinin receptor antagonists are useful in pathological conditions of the CNS.
激肽，包括缓激肽和胰激肽，是在组织损伤或炎症部位产生并发挥作用的肽类物质。它们通过激活与多种生化转导机制偶联的特定B1或B2受体，诱导多种效应。在周围组织中，激肽的作用包括血管舒张、血管通透性增加以及刺激免疫细胞和含肽感觉神经元，从而诱发疼痛和一些神经肽诱导的反射。中枢神经系统中也存在激肽合成机制，激肽可能在其中引发类似的一系列事件，包括血流量增加和血浆渗漏。激肽是神经和神经胶质组织的强效刺激物，可诱导其他促炎介质如前列腺素和细胞毒素（细胞因子、自由基、一氧化氮）的合成和释放。这些事件会导致神经组织损伤以及血脑屏障功能的长期紊乱。中枢神经系统创伤和缺血的动物模型表明，激肽活性的增加可通过激肽受体拮抗剂或抑制激肽产生来逆转。激肽还具有许多其他中枢作用，包括对大脑内（可能与血管性头痛有关）和脊髓背角内疼痛信号传导的影响，在脊髓背角，初级传入伤害感受器可被刺激。激肽似乎在心血管调节中也起作用，尤其是在慢性自发性高血压期间。然而，目前缺乏中枢神经系统病理生理条件下激肽释放的直接证据，除传入神经末梢外，脊髓或中枢神经元是否对激肽敏感也尚不清楚。有必要对激肽的作用及其中枢药理学进行更详细的研究。确定抑制激肽活性是否会减轻中枢神经系统炎症以及激肽受体拮抗剂在中枢神经系统病理状况下是否有用也很重要。
