THE ROLE OF BRADYKININ B-1 RECEPTORS IN THE MAINTENANCE OF INTRAARTICULAR PLASMA EXTRAVASATION IN CHRONIC ANTIGEN-INDUCED ARTHRITIS
THE ROLE OF BRADYKININ B-1 RECEPTORS IN THE MAINTENANCE OF INTRAARTICULAR PLASMA EXTRAVASATION IN CHRONIC ANTIGEN-INDUCED ARTHRITIS
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DOI：
10.1111/j.1476-5381.1994.tb17083.x
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发表时间：
1994-11-01
影响因子：
7.3
通讯作者：
KIDD, BL
中科院分区：
文献类型：
--
作者：
CRUWYS, SC;GARRETT, NE;KIDD, BL
1采用抗原诱导的大鼠慢性关节炎模型，研究缓激肽B-1和B-2受体在缓激肽和去精氨酸(9)缓激肽诱导的正常和炎症大鼠膝关节血浆渗出中的作用。对伊文思蓝提取技术的改进允许在该模型中评估非刺激性(基础)血浆外渗。研究了缓激肽B-1和B-2受体在基础滑膜血浆外渗中的作用。2在正常膝关节，关节内注射缓激肽(BK)可引起强的、剂量依赖的血浆外渗，其阈值为0.01nmol，ED(50)为0.1nmol。第5天膝关节炎。基础血浆外渗显著增强。较低剂量的BK没有明显的作用，在0.1nmoL时首次观察到高于基础渗出量的增加。3 B-1激动剂Des-Arg(9)-BK可引起正常膝关节轻微但显著的血浆外渗，但作用弱于缓激肽。这种反应被B-1受体拮抗剂Des-Arg(9)，[Leu(8)]-BK抑制。低剂量的Des-Arg(9)-BK缓激肽对第5天关节炎膝关节的基础渗漏没有显著增加，但与BK相比，最大反应显著增强。4 B-2拮抗剂HoE 140在0.0-1.0nmol剂量范围内抑制BK诱导的正常膝关节的血浆外渗，但在第5天炎症膝关节相对无效。B-1受体拮抗剂Des-Arg(9)，[Leu(8)]-BK在正常关节中相对无效，但在第5天对BK诱导的血浆外渗有增强作用。5 Hoe 140和Des-Arg(9)，[Leu(8)]-BK均以剂量依赖的方式抑制关节炎关节的基础渗出。虽然HOE 140在第1天是更有效的抑制剂，但它的效力低于Des-Arg(9)，[Leu(8)]-BK在第5.6天。虽然正常组织对BK的大部分反应是通过B-2受体介导的，但在正常关节组织中可能存在一小部分B-1受体。这项研究提供的数据表明，在炎症关节组织中，B-1受体在调节血浆外渗方面的作用正在演变。BK拮抗剂在治疗关节炎中的作用也被提出。
1 The role of bradykinin B-1 and B-2 receptors in bradykinin- and des-Arg(9)-bradykinin-induced plasma extravasation in normal and inflamed rat knee joints was investigated by use of an antigen-induced model of chronic arthritis. A modification of an Evans blue extraction technique allowed the unstimulated (basal) plasma extravasation to be assessed in this model. The contributions of bradykinin B-1 and B-2 receptors towards basal synovial plasma extravasation were determined.2 In normal knees, intra-articular injection of bradykinin (BK) induced plasma extravasation in a potent, dose-dependent manner with a threshold of 0.01 nmol and an ED(50) of 0.1 nmol. In day 5 arthritic knees. basal plasma extravasation was substantially enhanced. Lower doses of BK had no demonstrable effect and increases above basal extravasation were first observed at 0.1 nmol. Thereafter the dose-response mirrored the response in normal knees and the maximal response was unaltered.3 The B-1 agonist, des-Arg(9)-BK, induced slight but significant plasma extravasation in normal knees but was less potent than bradykinin. This response was inhibited by the B-1 receptor antagonist, des-Arg(9), [Leu(8)]-BK. Lower doses of des-Arg(9)-BK bradykinin did not significantly increase basal extravasation in day 5 arthritic knees but, in contrast to BK, the maximal response was significantly enhanced.4 The B-2 antagonist, Hoe 140, inhibited BK-induced plasma extravasation in normal joints over a dose-range of 0.0-1.0 nmol but was relatively inactive in day 5 inflamed knees. The B-1 receptor antagonist, des-Arg(9), [Leu(8)]-BK, was relatively inactive in normal joints but showed increased potency against BK-induced plasma extravasation in day 5 arthritic joints.5 Hoe 140 and des-Arg(9),[Leu(8)]-BK both inhibited basal extravasation in arthritic joints on days 1 and 5 post-challenge in a dose-dependent fashion. Whilst Hoe 140 was the more potent inhibitor on day 1, it was less potent than des-Arg(9),[Leu(8)]-BK on day 5.6 Although the majority of responses to BK in normal tissue are mediated via B-2 receptors, a small population of B-1 receptors may exist in normal joint tissues. The data presented in this study suggest an evolving role for B-1 receptors in the mediation of plasma extravasation in inflamed joint tissues. A role for BK antagonists in the treatment of arthritis is also suggested.