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

β3-肾上腺素受体（β3-AR）和Ca^<2+>敏感性大电导K^+通道（MaxiK.通道）是针对膀胱过度活动症的药物治疗的潜在靶点。在本研究中，为了研究它们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膀胱组织进行了基础研究，并将其结果与非膀胱平滑肌（气管和血管）的结果进行了比较。在本研究中，我们获得了以下新的发现.在豚鼠气管平滑肌中，我们检测到新型β_1-AR，其提供了pA_2值较低的β-AR拮抗剂.在大鼠主动脉平滑肌中检测到三种类型的β -AR（β_1-AR、β_2-AR、β_3-AR）。此外，我们还发现β_1-AR和β_2-AR的分布具有区域特异性。在豚鼠主动脉平滑肌中，首次检测到异丙肾上腺素（ISO）诱导的快速耐受性β-AR.在麻醉豚鼠模型上，分别采用气囊法和膀胱测压法建立膀胱动力学变化的记录系统，观察乙酰胆碱酯酶抑制剂对膀胱压力变化的影响.在豚鼠膀胱平滑肌中检测β_3-AR和MaxiK通道.在β_3-AR介导的抑制性调节豚鼠膀胱平滑肌张力中发现了“环腺苷酸非依赖性机制”。此外，在小鼠膀胱平滑肌中，MaxiK通道β_1亚基在β_3-AR介导的调节系统中发挥作用。

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.