INSERM, U1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Université Paul Sabatier , F-31432, Toulouse , France.
Expert Opin Ther Targets. 2013 Oct;17(10):1145-66. doi: 10.1517/14728222.2013.827664. Epub 2013 Aug 20.
Kinins are main active mediators of the kallikrein-kinin system (KKS) via bradykinin type 1 inducible (B1R) and type 2 constitutive (B2R) receptors. B2R mediates most physiological bradykinin (BK) responses, including vasodilation, natriuresis, NO, prostaglandins release.
The article summarizes knowledge on kinins, B2R signaling and biological functions; highlights crosstalks between B2R and renin-angiotensin system (RAS). The double role (Janus face) in physiopathology, namely the beneficial protection of the endothelium, which forms the basis for the therapeutical utilization of B2 receptor agonists, on the one side, and the involvement of B2R in inflammation or infection diseases and in pain mechanisms, which justifies the use of B2R antagonists, on the other side, is extensively analyzed.
For decades, the B2R has been unconsciously activated during angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) treatments. Whether direct B2R targeting with stable agonists could bring additional therapeutic benefit to RAS inhibition should be investigated. Efficacy, established in experimental models, should be confirmed by translational studies in cardiovascular pathologies, glaucoma, Duchenne cardiopathy and during brain cancer therapy. The other face of B2R is targeted by antagonists already approved to treat hereditary angioedema. The use of antagonists could be extended to other angioedema and efficacy tested against acute pain and inflammatory diseases.
激肽是激肽释放酶-激肽系统（KKS）的主要活性介质，通过缓激肽 1 型诱导（B1R）和 2 型组成型（B2R）受体发挥作用。B2R 介导大多数生理缓激肽（BK）反应，包括血管舒张、利钠、NO、前列腺素释放。
本文总结了激肽、B2R 信号转导和生物学功能的知识；强调了 B2R 与肾素-血管紧张素系统（RAS）之间的串扰。B2R 在病理生理学中的双重作用（两面性），即对内皮的有益保护，这是 B2 受体激动剂治疗应用的基础，一方面，以及 B2R 参与炎症或感染性疾病和疼痛机制，这证明了 B2R 拮抗剂的使用是合理的，另一方面，被广泛分析。
几十年来，B2R 在血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARB）治疗期间一直被无意识地激活。直接用稳定的激动剂靶向 B2R 是否能为 RAS 抑制带来额外的治疗益处，这一点值得研究。在心血管疾病、青光眼、杜兴氏心肌病和脑癌治疗中，应通过实验模型中的转化研究来验证已在实验模型中确立的疗效。B2R 的另一面由已被批准用于治疗遗传性血管性水肿的拮抗剂靶向。拮抗剂的使用可以扩展到其他血管性水肿，并针对急性疼痛和炎症性疾病进行疗效测试。
