Document Detail


Adenosine can mediate its actions through generation of reactive oxygen species.
MedLine Citation:
PMID:  20531463     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Debebe Gebremedhin; Brian Weinberger; David Lourim; David R Harder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-09
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  30     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-27     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1777-90     Citation Subset:  IM    
Affiliation:
Department of Physiology, Medical College of Wisconsin, Milwaukee, 53226, USA. mariyei@mcw.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analogs & derivatives,  metabolism*,  pharmacology
Animals
Antihypertensive Agents / pharmacology
Catalase / pharmacology
Cells, Cultured
Cerebral Arteries / cytology,  drug effects,  physiology*
Free Radical Scavengers / pharmacology
Gene Expression
Male
Muscle Cells / cytology,  metabolism*
Phenethylamines / pharmacology
Polyethylene Glycols / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P1 / genetics,  metabolism*
Superoxide Dismutase / pharmacology
Superoxides / analysis,  metabolism*
Vasodilation* / drug effects
Grant Support
ID/Acronym/Agency:
HL33833-18/HL/NHLBI NIH HHS; HL59996-07/HL/NHLBI NIH HHS; HL9210501A1/HL/NHLBI NIH HHS; R01 HL033833-26/HL/NHLBI NIH HHS; R01 HL092105-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Free Radical Scavengers; 0/Phenethylamines; 0/Polyethylene Glycols; 0/Receptors, Purinergic P1; 0/catalase-polyethylene glycol; 0/polyethylene glycol-superoxide dismutase; 11062-77-4/Superoxides; 120225-54-9/2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; 58-61-7/Adenosine; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase
Comments/Corrections

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