Clinical implications from studies of α1 adrenergic receptor knockout mice
Clinical implications from studies of α1 adrenergic receptor knockout mice
复制标题
DOI：
10.1016/j.bcp.2006.11.002
复制
发表时间：
2007-04-15
影响因子：
5.8
通讯作者：
Tsujimoto, Gozoh
中科院分区：
文献类型：
--
作者：
Koshimizu, Taka-aki;Tanoue, Akito;Tsujimoto, Gozoh
α1-肾上腺素能受体(α1-AR)在心血管和非心血管组织中调节着大量的生理功能。由于α1-AR家族的单个成员(α1A-、α1B-和α1D-AR)在大多数组织中具有重叠的表达谱，因此阐明单个α1-AR亚型的确切生理作用仍然是一个具有挑战性的任务。为了缓解这一限制，采用了基因打靶的方法来产生缺乏一个或两个阿尔法1-AR基因的突变小鼠。本文讨论了最近对这些突变小鼠品系的研究，重点讨论了α1-AR在中枢神经系统和下尿路中的作用。这两个主要组织对于开发针对α1-ARs的新治疗策略特别感兴趣。通过结合基因打靶技术和药理学工具，可以描述阿尔法1-AR亚型的具体作用。(C)2006 Elsevier Inc.保留所有权利。
alpha 1-Adrenergic receptors (alpha 1-ARs) modulate a large number of physiological functions in cardiovascular and noncardiovascular tissues. Because individual members of the alpha 1-AR family (alpha 1A-, alpha 1B-, and alpha 1D-ARs) have overlapping expression profiles in most tissues, elucidation of the precise physiological roles of individual alpha 1-AR subtypes remains a challenging task. To alleviate this constraint, a gene targeting approach has been employed to generate mutant mice lacking one or two alpha 1-AR genes. Recent studies on these mutant mouse strains are discussed in this article, with an emphasis on the role of alpha 1-AR in the central nervous system and lower urinary tracts. These are two major tissues of particular interest for the development of new therapeutic strategies targeted to the alpha 1-ARs. By combining gene targeting techniques with pharmacological tools, the specific roles of alpha 1-AR subtypes could be delineated. (c) 2006 Elsevier Inc. All rights reserved.