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.

进行这项研究是为了确定Rho-激酶抑制剂Y-27632和Fasudil对大鼠气管抗胆碱酯酶（抗CHE）诱导的收缩和磷脂酰肌醇反应的影响。使用大鼠气管环或切片进行了等距张力和[^3H]单磷酸（IP_1）的体外测量。 Y-27632几乎完全抑制了新斯基氨酸和吡啶脱位剂诱导的收缩，每种法30μm，而乙酰胆碱诱导的收缩的收缩并不完全抑制，即，y-27632和fasudil的56％被y-27632抑制了56％，在100μm上分别为51％。法苏迪对新生氨酸和乙酰胆碱诱导的收缩的抑制作用完全逆转了肌球蛋白磷酸酶抑制剂。新生氨酸诱导的IP1积累在100μm下通过Fasudil衰减。结果表明，抗ches通过激活Rho-kinase途径会导致气道平滑肌收缩。

项目成果

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.

Anticholine sterase dmgs 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 (in press)
• 作者: K.Irita;et al.;Shibata O
• 通讯作者: Shibata O

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

Saito M: "Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M_3 receptor in the rat"Anesth Analg. (in press). (2004)

Saito M：“甲氧氯普胺通过抑制大鼠毒蕈碱 M_3 受体导致气道平滑肌松弛”Anesth Analg。