Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning.
Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning.
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发表时间：
1992-07
影响因子：
3.6
通讯作者：
D. Bylund;H. Blaxall;L. Iversen;M. G. Caron;R. J. Lefkowitz;J. W. Lomasney
中科院分区：
文献类型：
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作者：
D. Bylund;H. Blaxall;L. Iversen;M. G. Caron;R. J. Lefkowitz;J. W. Lomasney
基于广泛的放射配基数据和更有限的功能数据，已经确定了α 2-肾上腺素能受体的三种药理学亚型。最近，通过分子克隆技术已经鉴定出了三个人类α 2-肾上腺素能受体基因或cdna。然而，药理学上确定的亚型与分子克隆鉴定的亚型之间的关系尚不清楚。为了解决这一问题，我们将通过分子克隆鉴定并在COS-7细胞中表达的受体的药理学特性与药理学定义的受体在其各自的原型组织或细胞系中的特性进行了比较。通过放射性配体结合法测定了12种亚型选择性α 2-肾上腺素能拮抗剂对α 2受体的亲和力（Ki值）。pKi值的相关分析表明，HT29细胞系中定义的α 2A亚型、新生大鼠肺中定义的α 2B受体和对体肾细胞系中定义的α 2C亚型分别对应于克隆的人α 2-C10、α 2-C2和α 2-C4受体亚型。
On the basis of extensive radioligand data and more limited functional data, three pharmacological subtypes of alpha 2-adrenergic receptors have been identified. More recently, three human genes or cDNAs for alpha 2-adrenergic receptors have been identified by molecular cloning. The relationship, however, among the pharmacologically defined subtypes and those identified by molecular cloning has not been clear. In order to resolve this issue, we have compared the pharmacological characteristics of the receptors identified by molecular cloning and expressed in COS-7 cells with the characteristics of the pharmacologically defined receptors in their respective prototypic tissue or cell line. The affinities (Ki values) of 12 subtype-selective alpha 2-adrenergic antagonists were determined for the alpha 2 receptor in the six preparations, by radioligand binding. Correlation analyses of the pKi values indicate that the alpha 2A subtype, as defined in the HT29 cell line, the alpha 2B receptor of the neonatal rat lung, and the alpha 2C subtype, as defined in an oppossum kidney cell line, correspond to the cloned human alpha 2-C10, alpha 2-C2, and alpha 2-C4 receptor subtypes, respectively.