Molecular cloning and functional studies of alpha_1 adrenoceptors
α_1肾上腺素受体的分子克隆和功能研究
基本信息
- 批准号:09470023
- 负责人:
- 金额:$ 7.49万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:1997
- 资助国家:日本
- 起止时间:1997 至 1998
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
alpha_1 Adrenoceptor plays important physiological roles in blood pressure, lipid metabolism, urinary tissues and central nervous system. In the present research project. we carried out molecular biological and classical pharmacological studies in order to clarify alpha_1 adrenoceptor functions.1 . Molecular cloning of rabbit alpha_1 adrenoceptor subtypes : We screened rabbit liver cDNA library and identified alpha_<1a> alpha_<1b> and alpha_<1d> subtypes. Rabbit alpha_<1b> and alpha_<1d> subtypes showed high homology and the same pharmacological characters to those of other species reported previously. However, three splice variants were identified in rabbit alpha_<1b> adrenoceptor, which had uniqe sequence in C-terminal and showed different tissue distribution in rabbit.2. Identification of native alpha_1 adrenoceptor subtypes : Native alpha_1 adrenoceptors were examined in radioligand binding and functional experiments and identified in the following tissues ; alpha_<1A> and alpha_<1L> in human prostate, alpha_<1L> in human urethra, alpha_<1B> in human aorta, alpha_<1A> and alpha_<1L> in rat prostate and rabbit iris.3. Functional analysis of alpha_1 adrenoceptors with cytosensor : Human alpha_<1a> alpha_<1b> and alpha_<1d> adrenoceptors were stably expressed in CHO cells and the extracellular acidification rate (EAR) was measured with cytosensor. EAR increased concentration-dependently in response to alpha agonists such as noradrenaline and clonidine. Detailed analyses of concentration-response urves revealed full agonist, partial agonist, spare receptor and propriety of Schild plot, showing that classical receptor theory is applicable to this system.
α_1肾上腺素能受体在血压、脂质代谢、泌尿系统和中枢神经系统等方面具有重要的生理功能。在目前的研究项目中。我们进行了分子生物学和经典药理学研究,以阐明α_1肾上腺素受体的功能。兔α_1肾上腺素受体亚型的分子克隆:筛选兔肝cDNA文库,鉴定出α_<1a>α_<1b>和α_α_<1d>亚型。兔α_<1b>和α_<1d>亚型与已报道的其他物种的α_和α_亚型具有高度的同源性和相同的药理学特征。而在兔α肾上腺素受体中发现了三种剪接变异体<1b>,它们的C端序列不同,在兔体内的组织分布也不同.天然α_1肾上腺素受体亚型的鉴定:在放射性配体结合和功能实验中检测天然α_1肾上腺素受体,并在以下组织中鉴定:人前列腺中的α_<1A>和α_,<1L>人尿道中的α_<1L>,<1B>人主动脉中的α_,<1A><1L>大鼠前列腺和兔虹膜中的α_和α_.细胞传感器对α_1肾上腺素能受体功能的研究:人α_<1a>α_<1b>和α_<1d>肾上腺素能受体在CHO细胞中得到稳定表达,细胞传感器测定细胞外酸化速率(acidizationrate,acidizationrate,acidizationrate)。对于去甲肾上腺素和可乐定等α激动剂,EAR呈浓度依赖性增加。对浓度-效应曲线的详细分析揭示了完全激动剂、部分激动剂、备用受体和Schild图的正确性,表明经典受体理论适用于该系统。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
Takahashi M.: "New alpha_1-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for human prostates than arteries" J.Urol.161. 1350-1354 (1999)
Takahashi M.:“新型 α_1-肾上腺素受体拮抗剂 JTH-601 对人类前列腺的亲和力比对动脉的亲和力高 10 倍以上”J.Urol.161。
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Hattori K.: "Identification of binding sites of bopindolol and its two metabolites with beta_1-adrenoceptors by molecular modeling : comparison with beta_2 adrenoceptors." Pharmacology. 58. 183-189 (1999)
Hattori K.:“通过分子模型鉴定波吲洛尔及其两种代谢物与 β_1 肾上腺素受体的结合位点:与 β_2 肾上腺素受体的比较。”
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M.Takahashi, T.Taniguchi, S.Murata, et al.: "New α_1-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for human prostates than arteries" Journal of Urology. 161. 1350-1354 (1999)
M.Takahashi、T.Taniguchi、S.Murata 等人:“新型 α_1-肾上腺素受体拮抗剂 JTH-601 对人类前列腺的亲和力比动脉高 10 倍”《泌尿学杂志》161. 1350-1354( 1999)
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S.Nakamura, T.Taniguchi, F.Suzuki, et al.: "Evaluation of α_1-adrenoceptors in the rabbit iris : pharmacological characterization and expression of mRNA." British Journal of Pharmacology. (in press). (1999)
S.Nakamura、T.Taniguchi、F.Suzuki 等人:“兔虹膜中 α_1-肾上腺素受体的评估:mRNA 的药理学特征和表达”(出版中)。
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Muramatsu I.: "Tamsulosin : alpha_1-adrenoceptor subtype-selectivity and comparison with terazosin." Jpn.J.Pharmacol.78. 331-335 (1998)
Muramatsu I.:“坦索罗辛:α_1-肾上腺素受体亚型选择性以及与特拉唑嗪的比较。”
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MURAMATSU Ikunobu其他文献
MURAMATSU Ikunobu的其他文献
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{{ truncateString('MURAMATSU Ikunobu', 18)}}的其他基金
Intracellular M1-muscarinic acetylcholine receptors in central nervous system
中枢神经系统细胞内 M1-毒蕈碱乙酰胆碱受体
- 批准号:
15K08250 - 财政年份:2015
- 资助金额:
$ 7.49万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Receptor-operated Ca influx and transmitter release
受体操作的 Ca 流入和递质释放
- 批准号:
20390068 - 财政年份:2008
- 资助金额:
$ 7.49万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification and pharmacome analysis of receptor phenotypes originated from a single gene
源自单个基因的受体表型的鉴定和药组分析
- 批准号:
17390064 - 财政年份:2005
- 资助金额:
$ 7.49万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on sympathetic purinergic transmission in blood vessels
血管内交感嘌呤能传递的研究
- 批准号:
61570097 - 财政年份:1986
- 资助金额:
$ 7.49万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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