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

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Jensen BC, Swigart PM, Montgomery MD, Simpson PC

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

Naunyn Schmiedebergs Arch Pharmacol. 2010 Dec;382(5-6):475-82. doi: 10.1007/s00210-010-0558-x. Epub 2010 Sep 22.

PubMed ID

20857090 [ View in PubMed

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Abstract

Alpha-1-adrenergic receptors (alpha1-ARs) regulate coronary arterial blood flow by binding catecholamines, norepinephrine (NE), and epinephrine (EPI), causing vasoconstriction when the endothelium is disrupted. Among the three alpha1-AR subtypes (alpha1A, alpha1B, and alpha1D), the alpha1D subtype predominates in human epicardial coronary arteries and is functional in human coronary smooth muscle cells (SMCs). However, the presence or function of alpha1-ARs on human coronary endothelial cells (ECs) is unknown. Here we tested the hypothesis that human epicardial coronary ECs express functional alpha1-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 alpha1B-subtype messenger ribonucleic acid (mRNA) was predominant in cultured human epicardial coronary ECs (90-95% of total alpha1-AR mRNA), and total alpha1-AR binding density in ECs was twice that in coronary SMCs. Functionally, NE and EPI through the alpha1B 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 alpha1-ARs on human coronary ECs and indicate that the alpha1B subtype is predominant. Our findings provide another potential mechanism for adverse cardiac effects of drug antagonists that nonselectively inhibit all three alpha1-AR subtypes.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Epinephrine	Alpha-1A adrenergic receptor	Protein	Humans	Yes	Agonist	Details
Epinephrine	Alpha-1B adrenergic receptor	Protein	Humans	Yes	Agonist	Details
Epinephrine	Alpha-1D adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details