Price D T, Chari R S, Berkowitz D E, Meyers W C, Schwinn D A
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Mol Pharmacol. 1994 Aug;46(2):221-6.
At least three subtypes of alpha 1-adrenergic receptors (alpha 1ARs) have been identified using molecular techniques (alpha 1a/d, alpha 1b, and alpha 1c), whereas two subtypes of alpha 1ARs have been identified pharmacologically (alpha 1A and alpha 1B); however, controversies exist regarding how these two classification schemes relate to each other. In an attempt to clarify some of the controversies regarding classification of alpha 1AR subtypes, we have re-evaluated the distribution of mRNA for the cloned alpha 1AR subtypes (alpha 1a/d, alpha 1b, and alpha 1c) in various rat tissues thought to express alpha 1AR subtypes, as well as the human neuronal cell line SK-N-MC (a recently described model for pharmacologically defined alpha 1AAR and alpha 1BAR subtypes), using sensitive ribonuclease protection assay techniques. Total RNA extracted from various rat tissues and SK-N-MC cells was hybridized with rat and human alpha 1AR subtype-specific probes, respectively. In contrast to previously reported Northern blot analyses, alpha 1cAR mRNA is expressed in many rat tissues. Expression of alpha 1cAR mRNA is highest in those tissues that have been previously characterized by radioligand binding as expressing the classical, pharmacologically defined alpha 1AAR. Likewise, the human neuronal SK-N-MC cell line, classically thought to express pharmacological alpha 1AAR and alpha 1BAR subtypes, expresses both alpha 1a/dAR and alpha 1cAR mRNA and no alpha 1bAR mRNA. Collectively, these data suggest that the cloned alpha 1cAR subtype may represent the pharmacological alpha 1AAR, and they have important implications for merging pharmacological and molecular classifications of alpha 1AR subtypes.
利用分子技术已鉴定出至少三种α1 - 肾上腺素能受体（α1ARs）亚型（α1a/d、α1b和α1c），而通过药理学方法鉴定出了两种α1ARs亚型（α1A和α1B）；然而，关于这两种分类方案如何相互关联存在争议。为了澄清关于α1AR亚型分类的一些争议，我们使用灵敏的核糖核酸酶保护分析技术，重新评估了克隆的α1AR亚型（α1a/d、α1b和α1c）的mRNA在各种被认为表达α1AR亚型的大鼠组织以及人神经母细胞瘤细胞系SK - N - MC（一种最近描述的药理学定义的α1AAR和α1BAR亚型模型）中的分布。从各种大鼠组织和SK - N - MC细胞中提取的总RNA分别与大鼠和人α1AR亚型特异性探针杂交。与先前报道的Northern印迹分析相反，α1cAR mRNA在许多大鼠组织中表达。α1cAR mRNA在那些先前通过放射性配体结合表征为表达经典药理学定义的α1AAR的组织中表达最高。同样，传统上认为表达药理学α1AAR和α1BAR亚型的人神经母细胞瘤细胞系SK - N - MC，表达α1a/dAR和α1cAR mRNA，而不表达α1bAR mRNA。总体而言，这些数据表明克隆的α1cAR亚型可能代表药理学α1AAR，并且它们对于合并α1AR亚型的药理学和分子分类具有重要意义。
