Role of PGE_2 and PGI_2 in Gastric Neural Emergency System

PGE_2和PGI_2在胃神经应急系统中的作用

• 批准号: 13672396
• 负责人: HAYASHI Hiromi
• 金额: $ 1.47万
• 依托单位: Kitasato 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672396/
• 关键词: neural emergency system; capsaicin; CGRP; gastric mucosal injury; prostaglandin I_2; IP receptor knockout mice; PGI2; 胃粘膜微小循環; エタノール胃粘膜傷害; EPレセプターノックアウトマウス; PGE2

Background: Administration of capsaicin also inhibited ethanol-induced gastric mucosal injury through the immediate release of calcitonin gene-related peptide (CGRP) from primary sensory neurons, which is called the neural emergency system. In the present study, we tested whether endogenous prostaglandin I2 also modulates cytoprotective action by capsaicin using IP knockout mice.Methods: The stomachs of prostaglandin I receptor knockout mice (IP-/-) or their wild-type mice (IP+/+), anesthetized with urethane (1.225 g/kg, ip), were doubly cannulated from the esophageal and duodenal sides, and the gastric mucosa was perfused (0.5 ml/min) with physiological saline. Perfusate was estimated at the end of each perfusion experiment. In some animals, CGRP-(8-37), a CGRP antagonist (3 mg/kg) or indomethacin 81 mg/kg) was intravenously injected before perfusion of 50% ethanol containing capsaicin.Results: Capsaicin inhibited injured area in a dose dependent manner. Fifty % ethanol containing cap … More saicin (480 μM) immediately increased intra-gastric levels of CGRP, although 50% ethanol alone did not. The protective action of capsaicin (480 μM) against ethanol was completely abolished by intravenous injection of CGRP-(8-37). Indomethacin also inhibited the protective action of capsaicin, and this was accompanied with reduced levels of intra-gastric CGRP. Intra-gastric levels in prostaglandin E_2 were not increased by capsaicin treatment, but those in 6-keto-prostagalandin F1α, a metabolite of prostaglandin I_2, were markedly increased. No protective action of capsaicin was observed in IP-/-, which lacked the ability to increase intragastric CGRP levels in response to ethanol containing capsaicin. The CGRP content of the stomach from untreated IP-/- did not differ from those in IP+/+.Conclusions: The present results suggest that endogenous prostaglandin I_2 enhances the protective action of the capsaicin-mediated neural emergency system against ethanol-induced gastric mucosal injury through the enhancement of CGRP release. Less

背景资料：辣椒素还通过初级感觉神经元立即释放降钙素基因相关肽（CGRP）抑制乙醇诱导的胃粘膜损伤，这被称为神经应急系统。在本研究中，我们使用IP敲除小鼠测试内源性前列腺素I2是否也调节辣椒素的细胞保护作用。前列腺素I受体敲除小鼠（IP-/-）或其野生型小鼠（IP+/+）的胃，用乌拉坦麻醉（1.225 g/kg，ip），从食管和十二指肠侧双重插管，用生理盐水灌注胃粘膜（0.5 ml/min）。在每个灌注实验结束时估计灌注液。在部分动物中，先静脉注射CGRP-（8-37）（3 mg/kg）或吲哚美辛（81 mg/kg），再灌注含辣椒素的50%乙醇。含50%乙醇的瓶盖 ...更多信息 480 μM的水杨酸立即增加胃内CGRP的水平，尽管单独的50%乙醇没有。辣椒素（480 μM）对乙醇的保护作用可被静脉注射CGRP-（8-37）完全消除。吲哚美辛也抑制辣椒素的保护作用，这是伴随着胃内CGRP的水平降低。辣椒素处理不增加胃内前列腺素E_2的含量，但显著增加前列腺素I_2的代谢产物6-keto-mesalandin F1α的含量。在IP-/-中没有观察到辣椒素的保护作用，IP-/-缺乏响应于含有辣椒素的乙醇而增加胃内CGRP水平的能力。结论：内源性前列腺素I_2通过促进CGRP的释放，增强辣椒素介导的神经应急系统对乙醇性胃粘膜损伤的保护作用。少

项目成果

Hiromi Hayashi, et al.: "Transient Prevention of Ethanol-Induced Gastric Lesion by Capsaicin Due to Release of Endogenous Calcitonin Gene-Related Peptide in Rats"Jpn. J. Pharmacol.. 86. 351-354 (2001)

Hiromi Hayashi等人：“辣椒素由于释放内源性降钙素基因相关肽而暂时预防大鼠中乙醇诱发的胃损伤”Jpn。

Katsuharu Boku, et al.: "Adaptive cytoprotecion mediated by prostaglandin I2 is attributable to sensitization of CGRP-containing sensory nerves"Gastroenterology. 120. 134-143 (2001)

Katsuharu Boku 等人：“前列腺素 I2 介导的适应性细胞保护可归因于含有 CGRP 的感觉神经的敏化”胃肠病学。

Hiromi Hayashi, et al.: "Transient Prevention of Ethanol-Induced Gastric Lesion by Capsaicin Due to Release of Endogenous Calcitonin Gene-Related Peptide in Rats"Jpn.J.Pharmacol.. 86. 351-354 (2001)

Hiromi Hayashi等人：“由于在大鼠中释放内源性降钙素基因相关肽而通过辣椒素暂时预防乙醇诱发的胃损伤”Jpn.J.Pharmacol..86.351-354(2001)

朴勝春, 他: "IPレセプターを介するCGRP遊離増大と胃粘膜損傷抑制作用"Ulcer Research. 28. 8-13 (2001)

Park Shen-chun 等：“IP 受体介导的 CGRP 释放增加和胃粘膜损伤的抑制”Ulcer Research 28. 8-13 (2001)。

Katsuharu Arai., et al.: "Endogenous Prostaglandin I2 Regulates Neural Emergency System through the Release of Calcitonin Gene-Related Peptide"Gut. (in press). (2003)

Katsuharu Arai., et al.：“内源性前列腺素 I2 通过降钙素基因相关肽的释放调节神经应急系统”Gut。