Studies on the finictional coupling between β3-adtenoceptor and MaxiK channel in urinary bladder smooth muscle

膀胱平滑肌β3-肌腱受体与MaxiK通道功能耦合的研究

基本信息

批准号：
18590157
负责人：
TANAKA Yoshio
金额：
$ 2.07万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

β3-Adrenoceptor (β3-AR) and Ca^<2+>-sensitive large conductance K^+ channel (MaxiK. channel) are potential targets for drug therapy against overactive bladder. In the present study, in order to investigate their possible functional coupling and to establish their molecular basis, we carried out fundamental studies using urinary bladder tissues of the guinea-pigs and mice, and compared their results with those of non-urinary bladder smooth muscles (trachea and blood vessels). In this study, we obtained the following new findings.1. In guinea-pig tracheal smooth muscle, we detected new types of (β_1-AR that provides (β-AR antagonists with lower pA_2 values.2. In rat aortic smooth muscle, we detected three types of β -AR (β_1-AR, β_2-AR, β_3-AR). Furthermore, we found that distribution of β_1-AR and β_2-AR is region-specific.3. In guinea-pig aortic smooth muscle, we firstly detected the β-ARs that shows tachyphylaxis with repeated exposure to isoprenaline (ISO).4. In the anaesthetized guinea-pig, we established recording systems for the changes of urinary bladder motility via balloon method and cystometry method, and investigated the effects of acetylcholinesterase inhibitors on the urinary bladder pressure changes.5. In guinea-pig urinary bladder smooth muscle, we detected β_3-AR and MaxiK channel.6. We found out "cyclic AMP-independent mechanism" in β_3-AR-mediated inhibitory regulation of guinea-pig urinary bladder smooth muscle tension. Furthermore, in mouse urinarybladder smooth muscle, MaxiK channel β_1-subunit plays a role in the β_3-AR-mediated regulatory system.

β3-肾上腺素受体（β3-AR）和Ca^<2+> - 敏感的大电导K^+通道（Maxik。Channel）是针对过度活跃膀胱的药物治疗的潜在靶标。在本研究中，为了研究其可能的功能耦合并建立其分子基础，我们使用豚鼠和小鼠的尿膀胱组织进行了基本研究，并将其结果与非尿液膀胱膀胱平滑肌（气管和血管）的结果进行了比较。在这项研究中，我们获得了以下新发现1。在豚鼠气管平滑肌中，我们检测到了（β_1-AR提供的新型类型的（β-AR拮抗剂）PA_2值较低。2。在大鼠主动脉平滑肌中，我们检测到三种β-AR（β_1-AR，β_2-ar，β_2-ar，β_2-ar，β_3-ar）。在豚鼠主动脉平滑肌中，我们首先检测到β-ars，该β-ARS在痛苦的豚鼠中反复暴露于等肾上腺素（ISO）。压力变化。5豚鼠尿液平滑的肌肉，我们检测到β_3-ar和maxik通道。6我们发现“与β_3armp的机制”。在β_3-ar介导的调节系统中。