权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

MOLECULAR BIOLOGICAL AND STRUCTURE-FUNCTION STUDIES OF CLOSTRIDIUM PERFRINGENS BETA-TOXIN

产气荚膜梭菌β-毒素的分子生物学和结构功能研究

基本信息

批准号：
13670286
负责人：
NAGAHAMA Masahiro
金额：
$ 2.3万
依托单位：
TOKUSHIMA BUNRI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. Tachykinin NK_<(1)> receptor antagonists, [D-Pro^<(2)>, D-Trp^<(7, 9)>]-SP, [D-pro^<(4)>, D-Trp^<(7, 9)>]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK_<(1)>, receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP_<(8-37)>). The toxin-induced leakage was significantly inhibited by the N-type Ca^<2+> channel blocker, omega-conotoxin MVIIA, and the bradykinin B_<(2)> receptor antagonist, HOE140 (D-Arg-[Hyp^<(3)>, Thi^<(5)>, D-Tic^<(7)>, Oic^<(8)>]-bradykinin), but was not affected by the selective L-type Ca^<2+> channel blocker, verapamil, the P-type Ca^<2+> channel blocker, omega-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na^+ channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK_<(1)> receptors.

产气荚膜梭菌β毒素导致动物背部皮肤坏死和水肿。在本研究中，我们研究了毒素引起水肿的机制。毒素诱导Balb/c小鼠背部皮肤中的血浆外渗。组胺1受体拮抗剂苯海拉明可明显抑制外渗。然而，毒素并没有引起组胺从小鼠肥大细胞瘤细胞的释放。速激肽NK_（1）受体拮抗剂[D-Pro^<（2）>，D-Trp^<（7，9）>]-SP，[D-Pro^<（4）>，D-Trp^<（7，9）>]-SP和Spantide均能剂量依赖性地抑制毒素诱导的细胞渗漏。非肽类速激肽NK_（1）受体拮抗剂SR_（140333）可明显抑制毒素诱发的渗漏。经辣椒素预处理的小鼠皮肤可明显减少毒素引起的渗漏，而经降钙素基因相关肽受体拮抗剂（CGRP_<（8-37）>）全身预处理的小鼠皮肤对毒素的渗漏无影响。N型Ca^<2+>通道阻断剂ω-芋螺毒素MVIIA和缓激肽B_<2>受体拮抗剂HOE 140可显著抑制毒素诱导的渗漏（D-Arg-[Hyp^<（3）>，Thi^<（5）>，D-Tic^<（7）>，Oic^<（8）>]-缓激肽），但不受选择性L-型Ca^<2+>通道阻断剂维拉帕米的影响，P型Ca^2+通道阻滞剂，ω-蛇毒IVA，河豚毒素（TTX），抗TTX的Na^+通道阻滞剂，卡马西平，或感觉神经传导阻滞剂，木质素。这些结果提示，β毒素引起的小鼠皮肤血浆外渗是通过速激肽NK_（1）受体介导的。