Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells.
Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells.
复制标题
DOI：
10.1007/s00210-010-0558-x
复制
发表时间：
2010-12
影响因子：
3.6
通讯作者：
Simpson, Paul C.
中科院分区：
文献类型：
--
作者：
Jensen, Brian C.;Swigart, Philip M.;Montgomery, Megan D.;Simpson, Paul C.
关键词：
α-1-肾上腺素能受体（α1-AR）通过结合儿茶酚胺、去甲肾上腺素（NE）和肾上腺素（EPI）来调节冠状动脉血流，当内皮被破坏时引起血管收缩。在三种α1-AR亚型（α1A、α1B和α1D）中，α1D亚型在人心外膜冠状动脉中占主导地位，并在人冠状动脉平滑肌细胞（SMC）中起作用。然而，α1-AR在人冠状动脉内皮细胞（EC）上的存在或功能尚不清楚。在这里，我们检验了人心外膜冠状动脉EC表达功能性α1-AR的假设。培养人心外膜冠状动脉内皮细胞进行了研究，采用定量实时逆转录聚合酶链反应，放射性配体结合，免疫印迹和3 H-胸苷掺入。在体外培养的人心外膜冠状动脉内皮细胞中，α1-AR mRNA以α 1B亚型为主（占总α1-AR mRNA的90-95%），其结合密度是平滑肌细胞的2倍。在功能上，NE和EPI通过α1B亚型激活EC中的细胞外信号调节激酶（ERK），刺激EC内皮型一氧化氮合酶（eNOS）的磷酸化，并增加脱氧核糖核酸（DNA）的合成。这些结果首次证实了人冠状动脉EC上的α1-AR，并表明α1B亚型占主导地位。我们的发现为非选择性抑制所有三种α1-AR亚型的药物拮抗剂的不良心脏效应提供了另一种潜在机制。
Alpha-1-adrenergic receptors (α1-ARs) regulate coronary arterial blood flow by binding catecholamines, norepinephrine (NE), and epinephrine (EPI), causing vasoconstriction when the endothelium is disrupted. Among the three α1-AR subtypes (α1A, α1B, and α1D), the α1D subtype predominates in human epicardial coronary arteries and is functional in human coronary smooth muscle cells (SMCs). However, the presence or function of α1-ARs on human coronary endothelial cells (ECs) is unknown. Here we tested the hypothesis that human epicardial coronary ECs express functional α1-ARs. Cultured human epicardial coronary artery ECs were studied using quantitative real-time reverse transcription polymerase chain reaction, radioligand binding, immunoblot, and 3H-thymidine incorporation. The α1B-subtype messenger ribonucleic acid (mRNA) was predominant in cultured human epicardial coronary ECs (90–95% of total α1-AR mRNA), and total α1-AR binding density in ECs was twice that in coronary SMCs. Functionally, NE and EPI through the α1B subtype activated extracellular signal-regulated kinase (ERK) in ECs, stimulated phosphorylation of EC endothelial nitric oxide synthase (eNOS), and increased deoxyribonucleic acid (DNA) synthesis. These results are the first to demonstrate α1-ARs on human coronary ECs and indicate that the α1B subtype is predominant. Our findings provide another potential mechanism for adverse cardiac effects of drug antagonists that nonselectively inhibit all three α1-AR subtypes.
登录
查看更多内容
影响因子：
24
作者：
Jensen, Brian C.;Swigart, Philip M.;Laden, Marie-Eve;DeMarco, Teresa;Hoopes, Charles;Simpson, Paul C.
通讯作者：
Simpson, Paul C.
影响因子：
4.5
作者：
Nishino, Y;Masue, T;Deguchi, T
通讯作者：
Deguchi, T
DOI：
10.1124/jpet.102.048553
发表时间：
2003-06-01
影响因子：
3.5
作者：
Chalothorn, D;McCune, DF;Piascik, MT
通讯作者：
Piascik, MT
影响因子：
8.3
作者：
Nakagami, H;Morishita, R;Ogihara, T
通讯作者：
Ogihara, T
影响因子：
15.9
作者：
Murohara, T;Asahara, T;Isner, JM
通讯作者：
Isner, JM