Eason M G, Liggett S B
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Mol Pharmacol. 1993 Jul;44(1):70-5.
At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but appear to be widely distributed in humans and display subtype-specific expression in some tissues.
目前，分子克隆和药理学研究已确定了三种人类α2 - 肾上腺素能受体（α2AR）亚型，即α2C10、α2C4和α2C2。由于中枢神经系统以外的组织α2AR表达定义不明确，将α2AR亚型与特定功能相关联受到了限制。有人提出α2C4的表达局限于大脑，α2C2仅在肝脏和肾脏中表达，而α2C10几乎在所有组织中都有表达。然而，这是基于对有限数量大鼠组织的研究或使用非物种特异性方法的研究。因此，为了确定α2C10、α2C4和α2C2的组织表达情况，我们对从20种人类组织中分离的总RNA进行逆转录，然后使用聚合酶链反应扩增α2AR cDNA。该技术有两个优点：高灵敏度，并且通过使用亚型特异性寡核苷酸引物和探针，可以区分α2AR亚型。所研究的组织包括主动脉、腔静脉、心脏（心外膜和心内膜）、肺、骨骼肌、肝脏、胰腺（头部和尾部）、脂肪（肾周和皮下）、肾脏（皮质和髓质）、前列腺、胃、回肠、空肠、结肠、肾上腺和脾脏。我们发现这些组织中的大多数都表达α2C10，例外的是胰腺头部、皮下脂肪、结肠和脾脏。然而，与其他研究明显不同的是，我们发现α2C4和α2C2亚型有丰富的表达。除肝脏、脂肪、胃和结肠外，在所有组织中都发现了α2C4的表达，除心外膜外，几乎在所有组织中都发现了α2C2的普遍表达。在所有研究的组织中，只有结肠和皮下脂肪表达单一α2AR亚型，即α2C2。因此，α2AR亚型并非局限表达，而是似乎在人类中广泛分布，并在某些组织中表现出亚型特异性表达。
