Document Detail


ATP hydrolysis pathways and their contributions to pial arteriolar dilation in rats.
MedLine Citation:
PMID:  21803949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ATP is thought to be released to the extracellular compartment by neurons and astrocytes during neural activation. We examined whether ATP exerts its effect of promoting pial arteriolar dilation (PAD) directly or upon conversion (via ecto-nucleotidase action) to AMP and adenosine. Blockade of extracellular direct ATP to AMP conversion, with ARL-67156, significantly reduced sciatic nerve stimulation-evoked PADs by 68%. We then monitored PADs during suffusions of ATP, ADP, AMP, and adenosine in the presence and absence of the following: 1) the ecto-5'-nucleotidase inhibitor α,β-methylene adenosine 5'-diphosphate (AOPCP), 2) the A(2) receptor blocker ZM 241385, 3) the ADP P2Y(1) receptor antagonist MRS 2179, and 4) ARL-67156. Vasodilations induced by 1 and 10 μM, but not 100 μM, ATP were markedly attenuated by ZM 241385, AOPCP, and ARL-67156. Substantial loss of reactivity to 100 μM ATP required coapplications of ZM 241385 and MRS 2179. Dilations induced by ADP were blocked by MRS 2179 but were not affected by either ZM 241385 or AOPCP. AMP-elicited dilation was partially inhibited by AOPCP and completely abolished by ZM 241385. Collectively, these and previous results indicate that extracellular ATP-derived adenosine and AMP, via A(2) receptors, play key roles in neural activation-evoked PAD. However, at high extracellular ATP levels, some conversion to ADP may occur and contribute to PAD through P2Y(1) activation.
Authors:
Francesco Vetri; Haoliang Xu; Lizhen Mao; Chanannait Paisansathan; Dale A Pelligrino
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-29
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-29     Completed Date:  2011-11-22     Revised Date:  2013-02-08    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1369-77     Citation Subset:  IM    
Affiliation:
Neuroanesthesia Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
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MeSH Terms
Descriptor/Qualifier:
5'-Nucleotidase / antagonists & inhibitors,  metabolism
Adenosine A2 Receptor Antagonists / pharmacology
Adenosine Triphosphate / analogs & derivatives,  metabolism,  pharmacology,  physiology*
Animals
Antigens, CD / metabolism
Apyrase / antagonists & inhibitors,  metabolism
Arterioles / physiology
Carbon Dioxide / metabolism
Dose-Response Relationship, Drug
Electric Stimulation
Female
Hydrolysis
Indicators and Reagents
Purinergic P2Y Receptor Antagonists / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P1 / drug effects
Receptors, Purinergic P2Y1 / drug effects
Sciatic Nerve / physiology
Vasodilation / physiology*
Grant Support
ID/Acronym/Agency:
HL-088259/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; 0/Adenosine A2 Receptor Antagonists; 0/Antigens, CD; 0/Indicators and Reagents; 0/Purinergic P2Y Receptor Antagonists; 0/Receptors, Purinergic P1; 0/Receptors, Purinergic P2Y1; 124-38-9/Carbon Dioxide; 56-65-5/Adenosine Triphosphate; EC 3.1.3.5/5'-Nucleotidase; EC 3.6.1.5/Apyrase; EC 3.6.1.5/CD39 antigen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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