Faculty Collaboration Database

Ecto-5'-nucleotidase, CD73, is an endothelium-derived hyperpolarizing factor synthase. Arterioscler Thromb Vasc Biol 2013 Mar;33(3):629-36

Date

01/05/2013

Pubmed ID

23288168

Pubmed Central ID

PMC3587694

DOI

10.1161/ATVBAHA.112.300600

Scopus ID

2-s2.0-84874395522 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

OBJECTIVE: Adenosine dilates human coronary arteries by activating potassium channels in an endothelial cell-independent manner. Cell surface ecto-5'-nucleotidase (CD73) rapidly dephosphorylates extracellular adenosine 5'-monophosphate to adenosine. We tested the hypothesis that coronary vasodilation to adenine nucleotides is mediated by an endothelial CD73-dependent, extracellular production of adenosine that acts as an endothelium-derived hyperpolarizing factor.

METHODS AND RESULTS: Videomicroscopy showed that adenine nucleotides, but not inosine, potently dilated and hyperpolarized human coronary arteries independent of nitric oxide, prostacyclin, and classical endothelium-derived hyperpolarizing factors, whereas endothelial denudation, adenosine receptor antagonism, adenosine deaminase, or CD73 blockers reduced vasodilations. Liquid chromatography-electrospray ionization-mass spectrometry revealed adenosine accumulation in perfusates from arteries in the presence of adenosine 5'-diphosphate. CD73 was localized on the cell surface of endothelial cells, but not of vascular smooth muscle cells, and its deficiency suppressed vasodilation of mouse coronary arteries to adenine nucleotides and augmented vasodilation to adenosine. Adenosine dose-dependently dilated and hyperpolarized human coronary arteries to a similar extent as adenosine 5'-diphosphate.

CONCLUSIONS: Coronary vasodilation to adenine nucleotides is associated with endothelial CD73-dependent production of extracellular adenosine that acts as an endothelium-derived hyperpolarizing factor by relaxing and hyperpolarizing underlying vascular smooth muscle cells via activating adenosine receptors. Thus, CD73 is a novel endothelium-derived hyperpolarizing factor synthase in human and mouse coronary arteries.

Author List

Ohta M, Toyama K, Gutterman DD, Campbell WB, Lemaître V, Teraoka R, Miura H

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

5'-Nucleotidase
Adenine Nucleotides
Adenosine
Adenosine Deaminase
Animals
Biological Factors
Chromatography, Liquid
Coronary Vessels
Dose-Response Relationship, Drug
Endothelial Cells
Enzyme Inhibitors
Female
GPI-Linked Proteins
Humans
Inosine Nucleotides
Male
Membrane Potentials
Mice
Mice, Knockout
Microscopy, Video
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Purinergic P1 Receptor Antagonists
Spectrometry, Mass, Electrospray Ionization
Vasodilation
Vasodilator Agents