Interaction of leukotrienes with other mediators in pathological models and its regulation by drags.

病理模型中白三烯与其他介质的相互作用及其药物调节。

• 批准号: 02454497
• 负责人: KATORI Makoto
• 金额: $ 4.16万
• 依托单位: Kitasato University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454497/
• 关键词: Leukotriene B_4; Leukotriene C_4; 5-Lipoxygenase; Adhesion Molecules; CD_<11>; CD_<18>; ICAM-1; Gastric Mucosal Injury; Kallikrein; 5-リポキシゲナーゼ阻害薬; 心筋梗塞; ザフスタンスP; 好中球血管外游走; ロイコトリエンB4; 好中球走化作用; 血管内皮細胞粘着; ロイコトリエンC4; 胃粘膜障害; 粘膜下微小循環; カプサイシン

1) NEUTROPHIL EXTRAVASATION: Vital microscopic analyses in microcirculation of hamster cheek pouch revealed that after topical application of leukotriene (LT) B_4 extravasated neutrophils by five steps. Adhesion on endothelial cells was initiated by membrane changes of neutrophils, occurred less than 4.5 sec after exposure of LTB_4 and was inhibited by an antibody against CD18, indicating that adhesion was induced not by newly synthesized protein, but by activation of adhesion molecules, CD_<11>/CD_<18>. Intra-arteriolar infusion of LTB_4 did not induce the adhesion, intra-venular infusion did it and the adhesion was inhibited by an antibody against ICAM-1, indicating that ICAM-1 is not induced in the tissue, but normally present in only venular endothelial cells.2) ETHANOL-INDUCED GASTRIC MUCOSAL INJURY: Vital microscopic observation of the submucosal microcirculation of rat stomach after exposure of the gastric mucosa to 30-50 % ethanol revealed that this injury was induced by constr … More iction of the collecting venules of the mucosa and subsequent congestion of the mucosal blood flow. LTC_4 was generated in the gastric wall after ethanol and exogenous LTC_4 applied on the mucosal microvasculature constricted the collecting venules. The mucosal type mast cells in the gastric mucosa were selectively stained by an antibody against 5-lipoxygenase. Substance P and CGRP were also increased in the gastric lumen after exposure to ethanol. Constriction of the collecting venules after ethanol was inhibited by pretreatment with capsaicin, but not by spantide, an old Substance P antagonist.3) AIRWAY RESISTANCE: Intravenous injection of LTC_4 and LTD_4 to guinea pigs increased airway resistance and secreted tissue kallikrein into the lumen of the respiratory tract with increased secretion. LTC_4 was more potent than LTD4. The kallikrein secretion was induced by release of thromboxane (TX) A_2 and acetylcholine successively. Bradykinin released by kallikrein formed a positive feed back loop for secretion of kallikrein by release of TXA_2 and acetylcholine. Less

1) 中性粒细胞外渗：对仓鼠颊囊微循环的重要显微镜分析表明，局部应用白三烯 (LT) B_4 后，中性粒细胞通过五个步骤外渗，通过中性粒细胞的膜变化引发内皮细胞粘附，发生在暴露后不到 4.5 秒。 LTB_4 并被 CD18 抗体抑制，表明粘附没有被诱导通过新合成的蛋白质，但通过粘附分子的激活，LTB_4的动脉内输注不诱导粘附，静脉内输注则诱导粘附，并且粘附被针对ICAM的抗体抑制。 -1，表明 ICAM-1 在组织中不被诱导，但通常仅存在于小静脉内皮细胞中。2) 乙醇诱导的胃粘膜损伤：将胃粘膜暴露于 30-50% 乙醇后，对大鼠胃粘膜下微循环的重要显微镜观察表明，这种损伤是由粘膜集合小静脉收缩和随后粘膜血液充血引起的。将乙醇和外源性LTC_4施加到收缩的粘膜微血管后，在胃壁中产生LTC_4。胃粘膜中的粘膜型肥大细胞被抗 5-脂氧合酶的抗体选择性染色，并且在暴露于乙醇后，胃腔中的 CGRP 也增加。用辣椒素预处理，但不使用斯潘肽（一种古老的 P 物质拮抗剂）。3) 气道阻力：静脉注射LTC_4和LTD_4对豚鼠的作用增加了气道阻力，并且将组织激肽释放酶分泌到呼吸道腔中，其分泌量比LTD4更有效。激肽释放酶的分泌是通过相继释放血栓素(TX)A_2和缓激肽来诱导的。激肽释放酶释放的激肽释放酶形成正反馈环，通过释放激肽释放酶来分泌激肽释放酶TXA_2和乙酰胆碱较少。

项目成果

M. Katori, et al: "Inhibition of Neutophil migration and mecrosis by a selective 5-lipoxygenase inhibitor in rat cardiac infarction." Eur. J. Pharmacol. (brief common). 183. 2256 (1990)

M. Katori 等人：“选择性 5-脂氧合酶抑制剂在大鼠心肌梗塞中抑制中性粒细胞迁移和坏死。”

西山 和男,他: "エタノール胃粘膜障害機序とそれに対する内因性プロスタグランジンの作用。" 炎症. 11. 27-31 (1991)

Kazuo Nishiyama 等人：“乙醇胃粘膜损伤的机制以及内源性前列腺素对其的影响”。11. 27-31 (1991)。

C.Shima,et al.: "A Stable metabolite,Arg-Pro-Pro-Gly-Phe,of Bradykinin in the degradation pathway in human plasma." Japanese Journal of Pharmacology. 60. 111-119 (1992)

C.Shima 等人：“缓激肽在人血浆降解途径中的稳定代谢物 Arg-Pro-Pro-Gly-Phe”。

Y.Suzuki,A.Ueno,M.Kawamura,K.Nishiyama,M.Katori and H.Okabe: "Prostaglandin levels in the rat resting gastric wall and enhancement of prostaglandin E_2 generation after administration of mild hyperosmotic saline solution into the gastric lumen." Eicosanoi

Y.Suzuki、A.Ueno、M.Kawamura、K.Nishiyama、M.Katori 和 H.Okabe：“将轻度高渗盐水溶液注入胃腔后，大鼠静息胃壁中的前列腺素水平和前列腺素 E_2 生成的增强

M.Katori,T.Oda and K.Nagai: "A site of action of dexamethasone on leukocyte extravastion in microcirculation." Agents and Actions. 29. 24-26 (1990)

M.Katori、T.Oda 和 K.Nagai：“地塞米松对微循环中白细胞外渗的作用位点。”