| Budget Amount *help |
¥3,230,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
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.
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