| A(3) adenosine receptor activation attenuates neutrophil function and neutrophil-mediated reperfusion injury. | |
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MedLine Citation:
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PMID: 10564145 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study tested the hypothesis that A(3) adenosine receptors inhibit neutrophil (PMN) function and PMN-mediated reperfusion injury. 2-Chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), an A(3) agonist, did not attenuate superoxide production or myeloperoxidase release from stimulated PMNs. However, Cl-IB-MECA reduced platelet-activating factor-stimulated PMN adherence to coronary endothelium at low concentrations: 52 +/- 27, 45 +/- 10, and 87 +/- 23 PMNs/mm(2) at 0.1, 1.0, and 10 nM vs. 422 +/- 64 PMNs/mm(2) with platelet-activating factor alone. This inhibition was not blocked by A(1) (5 microM KW-3902) or A(2a) (5 microM KF-21326) antagonists: 44 +/- 3 and 43 +/- 2 PMNs/mm(2), respectively. Endothelial pretreatment with 1 nM Cl-IB-MECA reduced PMN adherence, which was reversed by the A(3) antagonist MRS-1220 (100 nM). PMN-mediated reperfusion injury was initiated in isolated rabbit hearts by infusion of 28 x 10(6) PMNs/min for 10 min early in reperfusion. PMNs caused a significant decrease in recovery of left ventricular developed pressure and positive and negative time derivatives of pressure (23 +/- 3, 25 +/- 3, and 23 +/- 3% of baseline, respectively) vs. buffer-perfused hearts (43 +/- 7, 44 +/- 7, and 45 +/- 6%, respectively). Cl-IB-MECA (10 nM) given at reperfusion attenuated the PMN-mediated loss of contractile recovery (40 +/- 3, 46 +/- 5, and 42 +/- 4% of baseline). Cl-IB-MECA reduced myeloperoxidase release activity (5.3 +/- 0.6 absorbance units/min) and CD18-positive cells (54 +/- 9 cells/slide) compared with the untreated PMN group (17.9 +/- 1.7 absorbance units/min and 183 +/- 68 cells/slide). We conclude that Cl-IB-MECA attenuates reperfusion injury by decreasing PMN-endothelial cell interactions. These results suggest that the A(3) adenosine receptor may be a novel therapeutic target for treatment of myocardial ischemia and reperfusion. |
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Authors:
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J E Jordan; V H Thourani; J A Auchampach; J A Robinson; N P Wang; J Vinten-Johansen |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 277 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1999 Nov |
Date Detail:
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Created Date: 1999-12-20 Completed Date: 1999-12-20 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: H1895-905 Citation Subset: IM |
Affiliation:
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Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Crawford Long Hospital of Emory University, Atlanta, Georgia 30365, USA. jjordan@zeus.bwh.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arteries / metabolism, physiology Binding, Competitive COS Cells Cell Adhesion Cell Degranulation Coronary Vessels / metabolism, physiology Dogs Hemodynamics Myocardial Contraction Myocardial Reperfusion Injury / metabolism, physiopathology* Myocardium / enzymology Neutrophils / physiology* Peroxidase / metabolism Rabbits Receptors, Purinergic P1 / metabolism, physiology* Superoxides / metabolism Ventricular Function, Left |
| Grant Support | |
ID/Acronym/Agency:
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N01 MH-30003/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Purinergic P1; 11062-77-4/Superoxides; EC 1.11.1.7/Peroxidase |
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