Samadfam R, Teixeira C, Bkaily G, Sirois P, de Brum-Fernandes A, D'Orleans-Juste P
Department of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, Québec, J1H 5N4, Canada.
Br J Pharmacol. 2000 Apr;129(8):1732-8. doi: 10.1038/sj.bjp.0703225.
The aim of the present study was to investigate the contribution of bradykinin (BK) B(1) and B(2) receptors in a model of type III hypersensitivity, the reverse passive Arthus reaction (RPA), in wild-type mice and transgenic B(2) knockout littermates. BK (10 microg mouse(-1)) or bovine serum albumin (0.5 mg mouse(-1)) induced a sustained Evans blue extravasation for more than 80 min in naive or rabbit anti-bovine serum albumin-treated mice (RPA model), respectively. The response to the two stimuli was prevented by the B(2) receptor antagonist, HOE-140, but not by [Leu(8)]desArg(9)-BK (B(1) receptor antagonist). In contrast to the wild-type littermates, RPA and bradykinin were unable to trigger an increase in plasma extravasation in B(2) knockout mice. Furthermore, endothelin-1 (5 microg mouse(-1)) and a selective NK-1 receptor agonist [Sar(9),Met (O(2))(11)]-SP (20 microg mouse(-1)), triggered a significant increase in peritoneal plasma extravasation in both wild-type and B(2) knockout animals. A pretreatment with indomethacin (200 microg mouse(-1)) significantly reduced the RPA-induced but not the BK-induced increase in Evans blue extravasation. Furthermore, RPA, but not BK, triggered a significant indomethacin-sensitive increase in peritoneal prostaglandin E(2) content. Our results suggest a pivotal role for B(2) receptors in the mechanism of plasma extravasation which occurs during the reverse passive Arthus reaction in the mouse. Moreover, our results suggest an important contribution of prostanoids in the plasma leakage mechanisms triggered by RPA but not by bradykinin.
本研究旨在探讨缓激肽（BK）B(1)和B(2)受体在III型超敏反应模型——反向被动Arthus反应（RPA）中，对野生型小鼠和转基因B(2)基因敲除同窝小鼠的作用。BK（10μg/只小鼠）或牛血清白蛋白（0.5mg/只小鼠）分别在未处理或经兔抗牛血清白蛋白处理的小鼠（RPA模型）中诱导了超过80分钟的持续伊文思蓝外渗。B(2)受体拮抗剂HOE - 140可抑制对这两种刺激的反应，但[Leu(8)]desArg(9)-BK（B(1)受体拮抗剂）则不能。与野生型同窝小鼠不同，RPA和缓激肽无法在B(2)基因敲除小鼠中引发血浆外渗增加。此外，内皮素-1（5μg/只小鼠）和选择性NK - 1受体激动剂[Sar(9),Met (O(2))(11)]-SP（20μg/只小鼠）在野生型和B(2)基因敲除动物中均引发了显著的腹膜血浆外渗增加。用吲哚美辛（200μg/只小鼠）预处理可显著降低RPA诱导的而非BK诱导的伊文思蓝外渗增加。此外，RPA而非BK引发了对吲哚美辛敏感的腹膜前列腺素E(2)含量显著增加。我们的结果表明，B(2)受体在小鼠反向被动Arthus反应期间发生的血浆外渗机制中起关键作用。此外，我们的结果表明，前列腺素在RPA引发的而非缓激肽引发的血浆渗漏机制中起重要作用。
