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Effect of endogenous vasoactive substances on airway ciliary motility

内源性血管活性物质对气道纤毛运动的影响

基本信息

批准号：
12671463
负责人：
SHIRAKAMI Gotaro
金额：
$ 2.37万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671463/
关键词：
airway ciliated epithelial cells airway ciliary movement nitric oxide cyclic GMP guanylyl cyclase protein kinase G L-arginine propofol 気管繊毛上皮気管繊毛運動 β受容体サイクリックAMP プロテインキナーゼA フォスフォジエステラーゼ心房性ナトリウム利尿ペプチド

项目摘要

The role of nitric oxide (NO) in ciliary beat frequency (CBF) regulation in airway epithelial cells were studied using cultured rat tracheal epithelial cells. Images of ciliated cells were videotaped using a phase-contrast microscope. CBF was increased by NOC-12 and GSNO (NO donors), L-arginine (a NO precursor), 8-Br-cGMP, zaprinast (a cGMP-specific phosphodiesterase inhibitor), isoproterenol (a beta-receptor agonist), 8-Br-cAMP, amrinon (a phosphodiesterase type III inhibitor) and rolipram (a cAMP-specific phosphodiesterase inhibitor). The enhancement of CBF by L-arginine, 8-Br-cGMP, isoproterenol and 8-Br-cAMP was inhibited by L-NMMA (a NO synthase inhibitor), ODQ (a soluble guanylyl cyclase (sGC)-selective inhibitor) or KT5823 (a protein kinase G (PKG)-selective inhibitor). L-NMMA, ODQ or KT5823 alone did not change CBF. The enhancement of CBF by isoproterenol and 8-Br-cAMP was inhibited by KT5720 (a protein kinase A (PKA)-selective inhibitor). The production of NO using diaminofluo … More rescein (DAF, an indicator for NO) and its relationship with CBF were studied. The ciliated cells pretreated with DAF became fluorescent, but no fluorescence was detected in the cells without the pretreatment. The fluorescent intensity and CBF increased by L-arginine, not by D-arginine. The enhancements by L-arginine were nearly abolished by L-NMMA, not by D-NMMA. D-arginine, L-NMMA and D-NMMA alone did not change fluorescent intensity and CBF. There was a significant positive correlation between the increases of fluorescent intensity and CBF. These results demonstrate that rat tracheal clliated epithelial cells produce NO, NO stimulattes CBF in autocrine/paracrine manner, the NO-sGC-PKG pathway is involved in the regulation of ciliary motility, and that the pathway is involved in CBF stimulation via the beta-adrenoreceptor-cAMP-PKA pathway. The effect of propofol, an intravenous anesthetic, on CBF was investigated. Propofol stimulated CBF dose dependently. The enhancement of CBF by propofol was inhibited by L-NMMA, ODQ or KT5823. These results demonstrate that propofol stimulates CBF via the NO-sGC-PKG pathway. Less

采用体外培养的大鼠气管上皮细胞，研究一氧化氮（NO）在气道上皮细胞纤毛搏动频率（CBF）调节中的作用。用相差显微镜记录纤毛细胞的图像。CBF由NOC-12和GSNO （NO供体）、l -精氨酸（NO前体）、8-Br-cGMP、zaprinast （cgmp特异性磷酸二酯酶抑制剂）、异丙肾上腺素（β受体激动剂）、8-Br-cAMP、amrinon （III型磷酸二酯酶抑制剂）和罗利普兰（camp特异性磷酸二酯酶抑制剂）增加。l -精氨酸、8-Br-cGMP、异丙肾上腺素和8-Br-cAMP对CBF的增强作用被L-NMMA （NO合成酶抑制剂）、ODQ（可溶性观酰基环化酶（sGC）选择性抑制剂）或KT5823（蛋白激酶G （PKG）选择性抑制剂）抑制。单独使用L-NMMA、ODQ或KT5823对CBF没有影响。异丙肾上腺素和8-Br-cAMP对CBF的增强作用被KT5720（一种蛋白激酶a （PKA）选择性抑制剂）抑制。研究了一氧化氮指示剂DAF （diaminfluo…More rescein）的合成及其与脑血流的关系。经DAF预处理的纤毛细胞呈荧光，未经DAF预处理的纤毛细胞无荧光。l -精氨酸增加了荧光强度和CBF，而d -精氨酸没有增加。L-NMMA几乎消除了l -精氨酸的增强作用，而D-NMMA则没有。d -精氨酸、L-NMMA和D-NMMA均不改变荧光强度和CBF。荧光强度的增加与CBF呈显著正相关。这些结果表明，大鼠气管夹带上皮细胞产生NO， NO以自分泌/旁分泌方式刺激CBF， NO- sgc - pkg通路参与纤毛运动调节，该通路通过β -肾上腺素受体- camp - pka通路参与CBF刺激。研究了静脉麻醉药异丙酚对脑血流的影响。异丙酚刺激脑血流的剂量依赖性。L-NMMA、ODQ和KT5823均能抑制异丙酚对脑血流的增强作用。这些结果表明，异丙酚通过NO-sGC-PKG通路刺激CBF。少