RGD Reference Report - In vivo adenosine receptor preconditioning reduces myocardial infarct size via subcellular ERK signaling. - Rat Genome Database

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In vivo adenosine receptor preconditioning reduces myocardial infarct size via subcellular ERK signaling.

Authors: Reid, EA  Kristo, G  Yoshimura, Y  Ballard-Croft, C  Keith, BJ  Mentzer RM, JR  Lasley, RD 
Citation: Reid EA, etal., Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2253-9. Epub 2005 Jan 14.
RGD ID: 1582282
Pubmed: PMID:15653762   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.01009.2004   (Journal Full-text)

The protective effects of adenosine receptor acute preconditioning (PC) are well known; however, the signaling mechanism mediating this effect has not been determined in in vivo models. The purpose of this study was to determine the role of the extracellular signal-regulated kinase (ERK) pathway in mediating adenosine PC in in vivo rat myocardium. Open-chest rats were submitted to 25 min of coronary artery occlusion and 2 h of reperfusion. ERK activation was assessed by measuring total and dually phosphorylated p44/42 ERK isoforms in nuclear and/or myofilament, mitochondrial, cytosolic, and membrane fractions. Adenosine receptor PC with the A1/A2a agonist 1S-[1a,2b,3b,4a(S*)]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3 H-imidazo[4,5-b]pyridyl-3-yl]cyclopentane carboxamide (AMP-579) reduced infarct size from 49 +/- 3% to 29 +/- 3%, an effect that was blocked by the mitogen-activated protein kinase-ERK inhibitor U-0126. ERK isoforms were present in all fractions, with the greatest expression in the cytosolic fraction and the least in the mitochondrial fraction. AMP-579 treatment increased preischemic p44/42 ERK phosphorylation in all fractions 2.7- to 6.9-fold. Reperfusion increased ERK isoform activation in all fractions, but there were no differences between control and AMP-579 hearts. Preischemic increases in phospo-p44/p42 ERK with AMP-579 were blunted by U-0126, although only in mitochondrial and membrane compartments. The PC effects of AMP-579 on infarct size and ERK were blunted by both the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine and, surprisingly, the A2a antagonist ZM-241385. These results indicate that the unique adenosine receptor agonist AMP-579 exerts its beneficial effects in vivo via both A1 and A2a receptor modulation of subcellular ERK isoform signaling.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Mapk1  (mitogen activated protein kinase 1)

Genes (Mus musculus)
Mapk1  (mitogen-activated protein kinase 1)

Genes (Homo sapiens)
MAPK1  (mitogen-activated protein kinase 1)


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