| Project/Area Number |
17390064
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | University of Fukui |
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Principal Investigator |
MURAMATSU Ikunobu University of Fukui, Faculty of Medical Sciences, Professor (10111965)
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| Co-Investigator(Kenkyū-buntansha) |
MORISHIMA Shigeru University of Fukui, Faculty of Medical Sciences, Lecturing Associate Professor (50290911)
SUZUKI Fumiko University of Fukui, Faculty of Medical Sciences, Assistant Professor (80291376)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,550,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2005: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Ph armacome / a1L. adrenocentor / a1A adrenocentor / Knock-out mouse / lower urinary tract / 大脳皮質 / 受容体多型 / 前立腺 / ファルマコーム説 / 組織片結合実験法 |
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| Research Abstract |
Every protein such as a receptor or enzyme is biosynthesized according to one corresponding gene. However, after expression, proteins may be frequently modified by many factors innative cells and tissues, so that these proteins no longer exhibit a single property. We have proposed t hat all of such proteins occurring in native tissues are designated as the `pharmacome'. In this study, we performed pharmacome analysis of α1-adrenoceptor (AR). At first, we found a unique a1-AR mediating adrenergic contraction in lower urinary tract and named as a1 L-AR because of its low affinity for prazosin. The a1 L-AR was identified by binding approach with intact tissue segments but not with membrane preparations. Thus, aft-AR converted to a1A-AR up on homogenization, suggesting a possible relationship between the both a1-ARs. Then we examined the effects of knockout (KO) of a1 -ARs. In wild-type, a1B-KO and a1D-KO mice, a1 L-AR was identified in functional and binding studies. However, in a1 A-K0 mice, not only a1A-AR but also a1L-AR was abolished. From these results it is concluded that both a1A-and a 1L-ARs are derived from a1A-AR gene, indicating that different phenotypes are expressed from a single gene.
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