Faculty Collaboration Database

Adenosine can mediate its actions through generation of reactive oxygen species. J Cereb Blood Flow Metab 2010 Oct;30(10):1777-90

Date

06/10/2010

Pubmed ID

20531463

Pubmed Central ID

PMC3023402

DOI

10.1038/jcbfm.2010.70

Scopus ID

2-s2.0-77957709548 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

Adenosine is an important cerebral vasodilator, but mediating mechanisms are not understood. We investigated the expression of adenosine receptor subtypes in isolated cerebral arterial muscle cells (CAMCs), and their role in adenosine-induced superoxide (O(2)(-)) generation and reduction in cerebral arterial tone. Reverse transcriptase-PCR, western blotting, and immunofluorescence studies have shown that CAMCs express transcript and protein for A1, A(2A), A(2B), and A(3) adenosine receptors. Stimulation of CAMCs with adenosine or the A(2A) agonist CGS-21680 increased the generation of O(2)(-) that was attenuated by the inhibition of A(2A) and A(2B) adenosine receptor subtypes, or by the peptide inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase gp91ds-tat, or by the mitochondria uncoupler 2,4-dinitrophenol. Application of adenosine or CGS-21680 dilated pressure-constricted cerebral arterial segments that were prevented by the antioxidants superoxide dismutase (SOD) conjugated to polyethylene glycol (PEG) and PEG-catalase or by the A(2B) adenosine receptor antagonist MRS-1754, or by the mixed A(2A) and A(2B) antagonist ZM-241385. Antagonism of the A(2A) and A(2B) adenosine receptors had no effect on cerebral vasodilatation induced by nifedipine. These findings indicate that adenosine reduces pressure-induced cerebral arterial tone through stimulation of A(2A) and A(2B) adenosine receptors and generation of O(2)(-) from NADPH oxidase and mitochondrial sources. This signaling pathway could be one of the mediators of the cerebral vasodilatory actions of adenosine.

Author List

Gebremedhin D, Weinberger B, Lourim D, Harder DR

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

Adenosine
Animals
Antihypertensive Agents
Catalase
Cells, Cultured
Cerebral Arteries
Free Radical Scavengers
Gene Expression
Male
Muscle Cells
Phenethylamines
Polyethylene Glycols
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P1
Superoxide Dismutase
Superoxides
Vasodilation