title: Reduction of apoptosis in the amygdala by an A2A adenosine receptor agonist following myocardial infarction.
abstract: It has been observed that a cytokine synthesis inhibitor, pentoxifylline, prevents the apoptotic processes taking place in the amygdala following myocardial infarction. However, it is unknown if the cardioprotective effect of A(2A) adenosine receptor agonist, CGS21680, which reduces cytokine synthesis, would lead to such amygdala apoptosis regression. Thus, this study was designed to investigate whether cardioprotective A(2A) adenosine receptor activation reduces apoptosis in the amygdala following myocardial infarction. Anesthetized rats were subjected to left anterior descending coronary artery occlusion for 40 min, followed by 72 h of reperfusion. The A(2A) agonist CGS21680 (0.2 mug/kg/min i.v.) was administered continuously for 120 min, starting (1) five minutes prior to instituting reperfusion (Early) or (2) five minutes after the beginning of reperfusion (Late). After reperfusion, myocardial infarct size was determined and the amygdala was dissected from the brain. Infarct size was reduced significantly in the Early compared to the Control group (34.6 +/- 1.8% and 52.3 +/- 2.8% respectively; p < 0.05), with no difference compared to the Late group (40.1 +/- 6.1%). Apoptosis regression was documented in the amygdala of the Early group by an enhanced phosphatidylinositol 3-kinase-Akt pathway activation and Bcl-2 expression concurrently to a caspase-3 activation limitation and reduction in TUNEL-positive cells staining. On the other hand, amygdala TUNEL-positive cell numbers were not reduced in the Late group. Moreover, TNFalpha was significantly reduced in the amygdala of the Early group compared to the Control and Late groups. These results indicate that A(2A) adenosine receptor stimulation is associated with apoptosis regression in the amygdala following myocardial infarction.
authors.affiliation: Centre de Biomédecine, Hôpital du Sacré-Coeur de Montréal, 5400 boulevard Gouin Ouest, Montréal, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Boucher
authors.forename: B P
authors.initials: BP
authors.lastname: Wann
authors.forename: S
authors.initials: S
authors.lastname: Kaloustian
authors.forename: R
authors.initials: R
authors.lastname: Cardinal
authors.forename: R
authors.initials: R
authors.lastname: Godbout
authors.forename: G
authors.initials: G
authors.lastname: Rousseau
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000959:Antihypertensive Agents; C494828:Bax protein, rat; D010627:Phenethylamines; D019253:Proto-Oncogene Proteins c-bcl-2; D043705:Receptor, Adenosine A2A; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000241:Adenosine