Mechanisms of airway smooth muscle contraction : physio-pharmacologic factors and intracellular signaling pathway

气道平滑肌收缩机制：生理药理学因素和细胞内信号通路

• 批准号: 15591638
• 负责人: SHIBATA Osamu
• 金额: $ 1.79万
• 依托单位: Nagasaki University Hospital of Medicine and Dentistry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591638/
• 关键词: Anticholinesterases; Rho-kinase; Phosphatidylinositol; Muscarinic M3 receptor; Rat; 抗コリンエステラーゼ; Y-27632

This study was carried out to determine the effects of Rho-kinase inhibitors, Y-27632 and fasudil, on the anticholinesterase (anti-ChE)-induced contractile and phosphatidylinositol responses of rat trachea. In vitro measurements of isometric tension and [^3H] inositol monophosphate (IP_1) formed were conducted by using rat tracheal rings or slices. Neostigmine- and pyridostigmine-induced contractions were almost completely inhibited by Y-27632 and fasudil at 30 μM for each, while acetylcholine-induced contraction was inhibited incompletely, i.e., by 56% by Y-27632 and by 51% by fasudil, at 100 μM for each, respectively. The inhibitory effects of fasudil on neostigmine- and acetylcholine-induced contractions were completely reversed by calyculin-A, a myosin phosphatase inhibitor. Neostigmine-induced IP1 accumulation was attenuated by fasudil at 100 μM. The results suggest that anti-ChEs cause airway smooth muscle contraction in part through activation of the Rho-kinase pathway.

本研究旨在确定 Rho 激酶抑制剂 Y-27632 和法舒地尔对抗胆碱酯酶 (抗 ChE) 诱导的大鼠气管收缩和磷脂酰肌醇反应的影响。通过使用大鼠气管环或切片进行等长张力和形成的[^3H]肌醇单磷酸(IP_1)的体外测量。新斯的明和吡斯的明诱导的收缩几乎被 Y-27632 和法舒地尔分别在 30 μM 时完全抑制，而乙酰胆碱诱导的收缩则被不完全抑制，即分别在 100 μM 时 Y-27632 抑制了 56%，法舒地尔抑制了 51%。法舒地尔对新斯的明和乙酰胆碱诱导的收缩的抑制作用被肌球蛋白磷酸酶抑制剂花萼蛋白-A 完全逆转。 100 μM 法舒地尔可减弱新斯的明诱导的 IP1 积累。结果表明，抗 ChE 药物部分通过激活 Rho 激酶途径导致气道平滑肌收缩。

项目成果

Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.

抗胆碱酯酶药物通过 Rho 激酶途径刺激大鼠气管平滑肌收缩。

• 发表时间: 2006
• 期刊: Anesth Analg. 102
• 作者: Shibata O;Saito M;Yoshimura M;Yamaguchi M;Nishioka K;Makita T;Sumikawa K.
• 通讯作者: Sumikawa K.

Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea.

司来吉兰 (Selegiline) 是一种 MAO-B 抑制剂，可减弱大鼠气管中的气道平滑肌收缩。

• 发表时间: 2004
• 期刊: J Pharm Pharmacol 56
• 作者: Saito M;Shibata O;Yamaguchi M;Yoshimura M;Makita T;Niwa M;Sumikawa K.;入田和男;Yoshimura M
• 通讯作者: Yoshimura M

Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea

司来吉兰 (Selegiline) 是一种 MAO-B 抑制剂，可减弱大鼠气管中的气道平滑肌收缩

• 发表时间: 2004
• 期刊: J Pharm Pharmacol. 56
• 作者: Yoshimura M;Shibata O;Saito M;Yamaguchi M;Nishioka K;Makita T;Sumikawa K.
• 通讯作者: Sumikawa K.

Propofol attenuates ovalbumin-induced smooth muscle contraction of the sensitized rat trachea: Inhibition of serotonergic and cholinergic signaling

• DOI: 10.1213/01.ane.0000229853.01875.60
• 发表时间: 2006-09-01
• 期刊: ANESTHESIA AND ANALGESIA
• 影响因子: 5.7
• 作者: Yamaguchi, Masakazu;Shibata, Osamu;Sumikawa, Koji
• 通讯作者: Sumikawa, Koji

Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M3 receptor in the rat trachea

甲氧氯普胺通过抑制大鼠气管中的毒蕈碱 M3 受体而导致气道平滑肌松弛

• 发表时间: 2004
• 期刊: Anesth Analg 98
• 作者: J.Khotib;M.Narita;M.Suzuki;Y.Yajima;T.Suzuki;Saito M
• 通讯作者: Saito M