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

Jensen BC, Swigart PM, Montgomery MD, Simpson PC - Naunyn Schmiedebergs Arch. Pharmacol. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division, VA Medical Center, University of California, San Francisco, San Francisco, CA, USA.

ABSTRACT
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 (3)H-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.

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Related in: MedlinePlus

α1-AR stimulation increases DNA synthesis in coronary ECs. EC cultures were treated for 24 h with NE or EPI (1 nM–20 μM) in the presence of propranolol, and DNA synthesis was estimated by 3H-thymidine incorporation
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Fig4: α1-AR stimulation increases DNA synthesis in coronary ECs. EC cultures were treated for 24 h with NE or EPI (1 nM–20 μM) in the presence of propranolol, and DNA synthesis was estimated by 3H-thymidine incorporation

Mentions: These data indicated that an α1-AR, most likely the α1B, activated eNOS at Ser-1177 in human coronary artery ECs. However, we were unable to detect NO production in our cultures using the fluorophore DAF-2 or the Griess reagent.


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

Jensen BC, Swigart PM, Montgomery MD, Simpson PC - Naunyn Schmiedebergs Arch. Pharmacol. (2010)

α1-AR stimulation increases DNA synthesis in coronary ECs. EC cultures were treated for 24 h with NE or EPI (1 nM–20 μM) in the presence of propranolol, and DNA synthesis was estimated by 3H-thymidine incorporation
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991196&req=5

Fig4: α1-AR stimulation increases DNA synthesis in coronary ECs. EC cultures were treated for 24 h with NE or EPI (1 nM–20 μM) in the presence of propranolol, and DNA synthesis was estimated by 3H-thymidine incorporation
Mentions: These data indicated that an α1-AR, most likely the α1B, activated eNOS at Ser-1177 in human coronary artery ECs. However, we were unable to detect NO production in our cultures using the fluorophore DAF-2 or the Griess reagent.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division, VA Medical Center, University of California, San Francisco, San Francisco, CA, USA.

ABSTRACT
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 (3)H-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.

Show MeSH
Related in: MedlinePlus