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)中性粒细胞浸出：对金黄地鼠颊囊微循环的活体显微镜分析表明，局部应用白三烯B_4后，中性粒细胞可分五步外渗。中性粒细胞在内皮细胞上的粘附是由中性粒细胞膜的变化引起的，在LTB_4作用后4.5秒内发生，并被抗CD_（18）抗体抑制，表明粘附不是由新合成的蛋白质引起的，而是由粘附分子CD_（18）/CD_（18）的活化<11>引起的<18>。小动脉内灌注LTB_4不诱导粘附，小静脉内灌注则诱导粘附，粘附可被抗ICAM-1抗体抑制，表明ICAM-1在组织中不被诱导，而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：对大鼠胃粘膜暴露于30- 50%乙醇后胃粘膜下微循环的活体显微镜观察表明，这种损伤是由胃粘膜收缩引起的。 ...更多信息 粘膜集合小静脉的收缩和随后的粘膜血流的充血。当乙醇和外源性LTC_4作用于粘膜微血管收缩集合微静脉时，在胃壁产生LTC_4。胃粘膜中的粘膜型肥大细胞用抗5-脂氧合酶的抗体选择性染色。P物质和CGRP也增加后，暴露于乙醇的胃腔。用辣椒素预处理可抑制乙醇引起的集合小静脉收缩，而Spantide（一种古老的P物质拮抗剂）则不抑制。3）气道阻力：静脉注射LTC_4和LTD_4可增加豚鼠气道阻力，并使组织激肽释放酶分泌增加。LTC_4比LTD_4更有效。激肽释放酶的分泌是由血栓素（TX）A_2和乙酰胆碱的释放依次诱导的。激肽释放酶释放缓激肽，通过释放TXA_2和乙酰胆碱，形成正反馈环，促进激肽释放酶的分泌。少

项目成果

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。”

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。”