Studies on the finictional coupling between β3-adtenoceptor and MaxiK channel in urinary bladder smooth muscle
| Project/Area Number |
18590157
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Toho University |
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Principal Investigator |
TANAKA Yoshio Toho University, Faculty of Pharmaceutical Sciences, Associate Professor (60188349)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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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| Keywords | β_1-adrenoceptors / β_3-adrenoceptors / urinary bladder smooth muscle / cyclic AMP / MaxiK channel / overactive bladder / underactive bladder / acetvlcholinesterase inhibitor / ノルアドレナリン / プロプラノロール |
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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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Report
(3 results)
Research Products
(77 results)
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[Journal Article] Role of BK channels in testosterone-induced relaxation of the aorta in spontaneously hypertensive rats2007
Author(s)
Unemoto, T., Matsushita, M., Tamura, K., Tanaka, Y., Koike, K., Kogo, H
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Journal Title
Biological & Pharmaceutical Bulletin 30(8)
Pages: 1477-1480
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Different changes of plasma membrane β-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol2007
Author(s)
Horinouchi, T., Morishima, S., Tanaka, T., Suzuki, F., Tanaka, Y., Koike, K., Miwa, S., Muramatsu, I
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Journal Title
Life Sciences 81(5)
Pages: 399-404
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] β_1-Adrenoceptors are required for normal male sexual function2007
Author(s)
Sanbe, A., Tanaka, Y., Fujiwara, Y., Tsumura, H., Yamauchi, J., Cotecchia, S., Koike, K., Tsujimoto, G.,Tanoue, A
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Journal Title
British Journal of Pharmacology 152(3)
Pages: 332-340
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] K_v channels contribute to nitric oxide-and atrial natriuretic peptide-induced relaxation of a rat conduit artery2006
Author(s)
Tanaka Y, Tang G, Takizawa K, Otsuka K, Eghbali M, Song M, Nishimaru K, Shigenobu K, Koike K, Stefani E, Toro L.
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Journal Title
Journal of pharmacology and Experimental Therapeutics 317(1)
Pages: 341-354
Description
「研究成果報告書概要(和文)」より
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Peer Reviewed
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[Journal Article] K_v channels contribute to nitric oxide- and atrial natriuretic peptide-induced relaxation of a rat conduit artery2006
Author(s)
Tanaka, Y., Tang, G., Takizawa, K., Otsuka, K., Eghbali, M., Song, M., Nishimaru, K., Shigenobu, K., Koike, K., Stefani, E., Toro, L
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Journal Title
Journal of Pharmacology and Experimental Therapeutics 317(1)
Pages: 341-354
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pharmacological evaluation of plasma membrane β -adrenoceptors in rat hearts using the tissue segment binding method2006
Author(s)
Horinouchi, T., Morishima, S., Tanaka, T., Suzuki, F., Tanaka, Y., Koike, K., Muramatsu, I
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Journal Title
Life Sciences 79(10)
Pages: 941-948
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of distigmine, a long-acting cholinesterase inhibitor, on urinary bladder contractile functions assessed by using cystometry method in anesthetized guinea-pigs2006
Author(s)
Sekiya, S., Ookawa, N., Horinouchi, T., Tanaka, Y., Koike, K
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Journal Title
Pharmacometrics (Oyo Yakuri 70(1/2)
Pages: 29-34
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Roles of BK channel in the relaxant response of the aorta to testosterone in the spontaneously hypertensive rats2008
Author(s)
Unemoto, T., Matsushita, M., Tamura, K., Tanaka, Y., Koike, K., Kogo, H
Organizer
The 128th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Yokohama-City
Year and Date
2008-03-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Propranolol-sensitive β-adrenoceptors in rat abdominal aortic smooth muscle2007
Author(s)
Takahashi, H., Michikawa, H., Matsushita, M., Kasuya, Y., Tanaka, Y., Koike, K
Organizer
The 9th Oyo-Yakuri Symposium
Place of Presentation
Tokyo
Year and Date
2007-09-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ameliorating effects of acetylcholinesterase inhibitor on the lower urinary tract dysfunctions : comparison of the effects of distigmine and neostigmine2007
Author(s)
Sekiya, S., Seki, Y., Takahashi, H., Teraoka, A., Michikawa, H., Tanaka, Y., Koike, K
Organizer
The 127th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama-City
Year and Date
2007-03-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Comparison of the stimulatory effects of distigmine and neostigmine on the lower urinary tract functions in the guinea-pigs2007
Author(s)
Sekiya, S., Seki, Y., Takahashi, H., Teraoka, A., Michikawa, H., Tanaka, Y., Koike, K
Organizer
The 80th Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Nagoya-City
Description
「研究成果報告書概要(欧文)」より
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[Presentation] β_3-アドレナリン受容体と創薬2006
Author(s)
小池 勝夫、通川 広美、田中 芳夫
Organizer
第50回日本薬学会関東支部大会
Place of Presentation
新潟市
Year and Date
2006-10-14
Description
「研究成果報告書概要(和文)」より
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[Presentation] β_3-Adrenoceptors and drug discovery2006
Author(s)
Koike, K., Michikawa, H., Tanaka, Y
Organizer
The 50th Kanto Area Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Niigata-City
Year and Date
2006-10-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 排尿障害の薬物治療2006
Author(s)
小池 勝夫、田中 芳夫
Organizer
第8回応用薬理シンポジウム
Place of Presentation
千葉市
Year and Date
2006-09-13
Description
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