151 research outputs found

    Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells

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    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

    Roundtable: International Criminal Justice: More than the Sum of Its Parts?

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    Moderator: John Cary Sims, Professor of Law, McGeorge School of Law; Omar M. Dajani, Professor of Law and Co-Director of the Global Center, McGeorge School of La

    Roundtable: International Criminal Justice: More than the Sum of Its Parts?

    No full text
    Moderator: John Cary Sims, Professor of Law, McGeorge School of Law; Omar M. Dajani, Professor of Law and Co-Director of the Global Center, McGeorge School of La
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