Vascular permeability and vasodilation induced by the Loxosceles intermedia venom in rats:: Involvement of mast cell degranulation, histamine and 5-HT receptors
Vascular permeability and vasodilation induced by the Loxosceles intermedia venom in rats:: Involvement of mast cell degranulation, histamine and 5-HT receptors
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DOI：
10.1016/j.toxicon.2007.10.007
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发表时间：
2008-03-01
期刊：
影响因子：
2.8
通讯作者：
da Silva-Santos, J. Eduardo
中科院分区：
文献类型：
--
作者：
Rattmann, Yanna D.;Pereira, Carlos R.;da Silva-Santos, J. Eduardo
中间岩蛛毒（Loxoseelesintermedia）的局部和全身作用机制仍知之甚少。我们显示使用用伊文思蓝染料（50 mg/kg，i. v.）小剂量的LIV（0.1、0.3、1和3 μ g/部位）以剂量依赖性方式增加大鼠的血管渗透性，而消炎痛（5 mg/kg，腹腔注射）没有改变这一作用，阿托品（1 mg/kg，i. p.），HOE-140（2 mg/kg，s.c.）或SR 140333（0.3 mg/kg，i.p.）但异丙嗪（15 mg/kg，i. p.）完全避免;甲基麦角酰胺（2 mg/kg，i. p.）和化合物48/80（3 mg/kg/天，持续3天）。在苯肾上腺素收缩的主动脉环中加入累积浓度的LIV（0.1-5 μ g），导致部分（类似于40%）和内皮依赖性舒张，受到一氧化氮合酶抑制剂L-NAME（10 μ M）和L-NMMA（1 mM）以及鸟苷酸环化酶抑制剂亚甲蓝（100 μ M）和ODQ（10 μ M）的抑制。LIV诱导的舒张被化合物48/80（10 μ M）和吡拉明（一种选择性组胺H1受体拮抗剂; 100 μ M）消除，但不能被阿托品（1 μ M）和吲哚美辛（10 μ M）消除。我们的研究结果表明，LIV增加血管通透性，诱导血管舒张。这些作用的发生是由于其能够使肥大细胞去活化并释放介质如组胺和组胺酸。(c)2007爱思唯尔有限公司保留所有权利。
The mechanisms involved in both local and systemic effects of Loxoseeles intermedia (brown spider) venom (LIV) are still poorly understood. We show using rats treated with Evans blue dye (50 mg/kg, i.v.) that small doses of the LIV (0.1, 0.3, 1 and 3 mu g/site) dose-dependently increase the vascular permeability in rats, an effect unchanged by indomethacin (5 mg/kg, i.p.), atropine (1 mg/kg, i.p.), HOE-140 (2 mg/kg, s.c.) or SR 140333 (0.3 mg/kg, i.p.), but fully avoided by promethazine (15 mg/kg, i.p.); methysergide (2 mg/kg, i.p.) and compound 48/80 (3 mg/kg/day for 3 days). Addition of cumulative concentrations of LIV (0.1-5 mu g) in phenylephrine-contracted aortic rings resulted in a partial (similar to 40%) and endothelium-dependent relaxation, inhibited by the nitric oxide synthase inhibitors L-NAME (10 mu M) and L-NMMA (1 mM), and the guanylate cyclase inhibitors methylene blue (100 M) and ODQ (10 mu M). LIV-induced relaxation was abolished by compound 48/80 (10 mu M) and pyrilamine (a selective histamine H1 receptor antagonist; 100 mu M), but not by atropine (1 mu M) and indomethacin (10 mu M). Our results disclose that LIV increases vascular permeability and induces vascular relaxation. These effects occur due to its ability to degranulate mast cells and release mediators such as histamine and serotonine. (c) 2007 Elsevier Ltd. All rights reserved.