| Project/Area Number |
08457421
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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 |
Urology
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| Research Institution | UNIVERSITY of TOKYO |
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Principal Investigator |
KAWABE Kazuki The University of Tokyo, Urology, Professor and Chairman, 医学部・附属病院, 教授 (20124670)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Takumi The Mitui Memorial Hospital, Urologist, 医員 (90167487)
KAMEYAMA Shuji The University of Tokyo, Urology, Assistant Professor, 医学部・附属病院, 講師 (90186015)
MORIYAMA Nobuo The University of Tokyo, Urology, Assistant Professor, 医学部・附属病院, 講師 (80143501)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Human prostate / Human prostatic urethra / alpha_1-adrenergic receptor / Binding experiment / Protection assay / α_1-アドレナリン受容体 / 前立腺肥大症 / 細胞培養 / in vitro autoradiography |
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| Research Abstract |
A) Identification of alpha_1-adrenoceptor subtype in the human prostatic urethra
1. To identify the alpha_1-adrenoceptor subtypes in the human prostatic urethra, we compared the potencies of various alpha_1-adrenoceptor agonists and antagonists in inhibiting [^3H] tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the binding of [^<125>] HEAT to cloned human alpha_<1a>, alpha_<1b> and alpha_<1d>.
2. The alpha_<1A>a-selective antagonists 5-methylurapidil and niguldipine showed higher affinities for both cloned alpha_<1a> and urethral alpha_1-adrenoceptorrs than for cloned alpha_<1b> and alpha_<1d>-adrenoceptors. alpha_<1A>- selective agonist also showed high affinity for the cloned alpha_<1a> subtype and urethral alpha_1-adrenoceptors. Prazosin showed lower affinity for alpha_1- adrenoceptors in the human prostatic urethra than for any of the three cloned alpha_1-adrenoceptors.
3. Comparison of the affinities of alpha_1-adrenoceptor agonists and ant
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agonistws for human prostatic urethral alpha_1-adrenoceptors to their affinities for the three cloned alpha_1-subtypes indicated a close correlation between the affinities for human urethral alpha_1- and the cloned alpha_<1a>-adrenoceptors. However, prazosin did not conform to this pattern. These findings suggest that the predominant alpha_1-adrernoceptor in the human urethra is the alpha_<1A> subtype, and that an alpha_<1L> subtype which has been characterised by its low affinity for prazosin, may also be present.
B) Quantification and distribution of alpha_1-adrenoceptor subtype mRNAs in mate prostatic urethra.
1. We performed RNase protection assays and in situ hybridization to investigate the ratio of the three alpha_1-adrenoceptor subtype mRNAs, alpha_<1a, 1b, 1d> in the male human posterior urethra, and their localization in urethral cross-sections. As revealed by the RNase protection assays, alpha_<1a> was the predominant subtype mRNA in male prostatic urethral samples. alpha_<1d.1b> mRNA was was not detected in any of the samples tested. The ratio of the abundances of the subtype mRNAs, alpha_<1a> : alpha_<1b> : alpha_<1d>, was 100 : 0 : 0 in the male prostatic urethra.
2. Intense alpha_<1a> staining observed in the smooth muscle of the urethra, but alpha_<1b> and alpha_<1d> staining was much less intense.
3. Of the three cloned al subtypes, alpha_<1a> is the most likely to be responsible for the contraction of the human prostatic urethra. Therefore alpha_<12> selective drugs may be more efficacious than nonselective drugs for the treatment of urethral disorders. Less
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