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Fundamental research for an inhalational therapy using hyposmotic solution to stimulate airway ciliary motility

使用低渗溶液刺激气道纤毛运动的吸入疗法的基础研究

基本信息

批准号：
16590169
负责人：
NAKAHARI Takashi
金额：
$ 2.24万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590169/
关键词：
airway epithelia mucrociliary clearance cilia ATP ciliary beat frequency (CBF)video micoscopy trachea bronchiole tracea ciliary beat frequency (CBF)purinergic receptor hypo-osmotic stress osmotic swelling cetylcholine

项目摘要

The ciliary beat frequency (CBF) of rat tracheal ciliary cells in a slice preparation was measured using video-enhanced contrast (VEC) microscopy. Acetylcholine (ACh) or ATP increased CBF mediated via intracellular Ca^<2+> concentration ([Ca^<2+>]_i) in a dose-dependent manner. An adequate hypo-osmotic stress (-40mosM) potentiated ACh-stimulated CBF increase in tracheal ciliary cells. The present study demonstrated that suramin (an inhibitor of purinergic receptors) and apyrase (an ATPase/ADPase) eliminate the hypo-osmotic potentiation of ACh-stimulated CBF increase and that ATP potentiates ACh-stimulated rises in [Ca^<2+>]_i and CBF increase. A hypo-osmotic stress (-40mosM) transiently increased [Ca^<2+>]_i and potentiated the ACh-stimulated [Ca^<2+>]_i increase. The hypo-osmotic potentiation of ACh-stimulated CBF increase was not detected under Ca^<2+>-free conditions. These observations suggest that a hypo-osmotic stress stimulates ATP release from the trachea. The released ATP may induce further increases in [Ca^<2+>]_i and CBF in ACh-stimulated tracheal ciliary cells, which may be mediated by purinergic receptors. On the other hand, in distal airway ciliary cells (lung slice) unlike trachea, ACh or ATP did not increase CBF and [Ca^<2+>]_i, although a Ca^<2+>-free solution decreased CBF, and ionomycin (5μM) or thapsigargin (2μM) increased it. Terbutaline (10μM), a selective β_2-adrenergic agonist, increased CBF in both tracheal and distal airway ciliary cells. These observations suggest that the Ca^<2+>-mobilization mechanisms via purinergic or muscarinic receptors of the distal airway ciliary cell may be different from those of the tracheal ciliary cell. Thus, the CBF increase is differently regulated in the tracheal and distal airway epithelia of the rat.

用视频增强对比显微镜（VEC）测定了大鼠气管纤毛细胞的纤毛搏动频率（CBF）。乙酰胆碱（ACh）或ATP均能剂量依赖性地增加脑血流量，其作用机制与细胞内Ca^2+浓度（[Ca^2+] i）有关。适当的低渗应激（~ 40 mosM）可增强ACh刺激的气管纤毛细胞CBF的增加。本研究表明，苏拉明（一种嘌呤能受体抑制剂）和腺苷三磷酸双磷酸酶（一种ATP酶/腺苷三磷酸酶）可消除ACh引起的脑血流量增加的低渗增强作用，而ATP可增强ACh引起的[Ca^<2+>]_i和脑血流量增加。低渗胁迫（-40mosM）使[Ca^<2+>]_i瞬时升高，并增强ACh刺激的[Ca^<2+]_i升高。在无Ca^<2+>条件下，未检测到ACh刺激CBF增加的低渗增强作用。这些观察结果表明，低渗应激刺激ATP从气管释放。释放的ATP可引起ACh刺激的气管纤毛细胞内[Ca^<2+>] i和CBF的进一步增加，这可能是由嘌呤能受体介导的。与气管不同的是，ACh或ATP不增加远端气道纤毛细胞的CBF和[Ca^2+] i，但无Ca^2+溶液可降低CBF，离子霉素（5μM）或毒胡萝卜素（2μM）可增加CBF，选择性β 2肾上腺素能激动剂特布他林（10μM）可增加气管和远端气道纤毛细胞的CBF。这些观察结果表明，远端气道纤毛细胞通过嘌呤能或毒蕈碱受体的Ca^2+动员机制可能不同于气管纤毛细胞。因此，在大鼠的气管和远端气道上皮中，CBF增加受到不同的调节。

项目成果

期刊论文数量（44）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cyclic GMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells.

豚鼠胃窦粘液细胞中乙酰胆碱刺激的胞吐作用的循环 GMP 调节。

DOI：
发表时间：
2006
期刊：
Am J Physiol Gastrointest Liver Physiol 290
影响因子：
0
作者：
Saad AH;Shimamoto C;Nakahari T;Fujiwara S;Katsu K and Marunaka Y.
通讯作者：
Katsu K and Marunaka Y.

Maintenance of olfactory neurogenesis requires HSFI, a major heat shock transcription factor in mice.

嗅觉神经发生的维持需要 HSFI，这是小鼠体内的一种主要热休克转录因子。

DOI：
发表时间：
期刊：
Journal of Biological Chemistry (in press)
影响因子：
0
作者：
Takaki E;Fujimoto M;Sugahara K;Nakahari T;Yonemura S;Tanaka Y;Hayashida N;Inouye S;Takemoto T;Yamashita H;Nakai A.
通讯作者：
Nakai A.

Cell shrinkage evoked by Ca2+-free solution in rat alveolar type II cells:: Ca2+ regulation of Na+-H+ exchange