A study on function mechanism of a novel endogenous

一种新型内源性激素的作用机制研究

• 批准号: 07672481
• 负责人: HAZATO Tadahiko
• 金额: $ 1.41万
• 依托单位: THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672481/
• 关键词: Enkephalin; Spinorphin; Aminopeptidase N; Leuhistin; Anti-inflammatory; Aminopeptidase N; Enkephalin調節因子; 好中球機能; 炎症制御機構

Spinorphin is a novel endogenous pain-regulated substance whic modulated an enkephalin-degrading activity. In this study, we found that spinorphin causes a significant inhibition of inflammatory responses by human PMNs stimulated with FMLP and may be a new endogenous anti-inflammatory peptide which is mediated in part through the suppression in [Ca^<2+>] i changes. Next we examined the effects of spinorphin, using an in vivo system involving mouse air-pouch as a model of acute inflammatory response. In this model carrageenan and PMNs accumulation at inflammatory sites was an indicator of an acute inflammatory response. Intravenous administration of spinorphin within air-pouch site elicited by carrageenan, the inhibition being 64%, compared to the saline-treated group. Combination of leuhistin, an inhibitor of aminopeptidase N,significantly suppressed PNMs accumulation induced carrageenan. In the future, spinorphin will be an important tool for use in clarifying of neuropeptide-induced biological phenomena such as enkephalin mediated pain and inflammation.

多诺芬是一种新型的内源性疼痛调节物质，可调节脑啡肽降解活性。在本研究中，我们发现Spin对FMLP刺激的人PMN的炎症反应有明显的抑制作用，可能是一种新的内源性抗炎肽，其部分机制是通过抑制[Ca^&lt；2+&gt；]i的变化来实现的。接下来，我们使用小鼠气囊作为急性炎症反应的模型，研究了Spin的作用。在该模型中，炎症部位角叉菜胶和中性粒细胞的聚集是急性炎症反应的指标。与生理盐水组比较，角叉菜胶诱导的气囊处静脉注射Spin的抑制率为%。联合应用氨基肽酶N抑制剂亮氨酸可显著抑制角叉菜胶诱导的PNMS积聚。在未来，Spin将成为阐明神经肽诱导的生物现象(如脑啡肽介导的疼痛和炎症)的重要工具。

项目成果

Tadahiko Hazato: "A study on anti-inflammatory effect of an endogenous pain-regulated substance・Spinorphin." Folia Pharmacol. Jpn.108, Supp 1. 155-160 (1996)

Tadahiko Hazato：“内源性疼痛调节物质·Spinolinphin 的抗炎作用的研究。”Jpn.108，Supp 1. 155-160 (1996)

Tadahiro Kanazawa: "Spinorphin, a novel endogenous regulator of enkephalin, in a model of acute inflammation" JPN.J.Pharm. 71. 247 (1996)

Tadahiro Kanazawa：“Spinorphin，一种新型内源性脑啡肽调节剂，在急性炎症模型中”JPN.J.Pharm。