Bès Sandrine, Ponsard Blandine, El Asri Mounia, Tissier Cindy, Vandroux David, Rochette Luc, Athias Pierre
Laboratory of Physiopathology and Pharmacology, Institute of Cardiovascular Research, University Hospital Center, 2 Boulevard Maréchal de Lattre de Tassigny, 21034 Cedex, Dijon, France.
Eur J Pharmacol. 2002 Oct 4;452(2):145-54. doi: 10.1016/s0014-2999(02)02295-1.
This work aimed to detect functional adenosine receptors in isolated rat cardiomyocytes and to study the influence of stimulation of these receptors in an in vitro model of ischemia. Cultures of cardiomyocytes were prepared from newborn rat ventricles. The contractions were photometrically monitored. In this preparation, adenosine induced a positive chronotropic response. This effect was reproduced by CGS 21680 (2-(4-[2-carboxyethyl]-phen-ethyl-amino) adenosine-5'N-ethylunosamide), a specific adenosine A(2) receptor agonist, and antagonized by DMPX (3,7-dimethyl-1-propargylxanthine), an adenosine A(2) receptor antagonist. However, R-PIA (R-N(6)-(2-phenylisopropyl)-adenosine; a specific adenosine A(1) receptor agonist) induced a negative chronotropic effect that was abolished by its corresponding adenosine A(1) antagonist DPCPX (1,3-dipropyl-8-cyclo-pentyl-adenosine). Substrate-free hypoxia, as simulation of ischemia, induced a progressive decrease and then arrest of spontaneous cell contractions. The spontaneous rhythmic contractile activity was restored during reoxygenation following simulated ischemia. Adenosine A(1) receptor stimulation with R-PIA induced a decrease of hypoxia-induced damage. This effect was antagonized by DPCPX, an adenosine A(1) receptor antagonist. Conversely, the cells treated with CGS 21680 did not display complete recovery after reoxygenation. In addition, this effect was abolished by DMPX, since the cells recovered normal function after reoxygenation. To conclude, it appeared that cardiomyocytes possess both functional adenosine A(1) and A(2) receptors and that only the activation of adenosine A(1) receptor had a cytoprotective effect against simulated ischemia-induced cardiac cell injury.
这项研究旨在检测分离的大鼠心肌细胞中的功能性腺苷受体，并在体外缺血模型中研究刺激这些受体的影响。从新生大鼠心室制备心肌细胞培养物。通过光度法监测收缩情况。在该制备物中，腺苷诱导了正性变时反应。这种效应可被特异性腺苷A(2)受体激动剂CGS 21680（2-(4-[2-羧乙基]-苯乙基-氨基)腺苷-5'-N-乙基尿苷）重现，并被腺苷A(2)受体拮抗剂DMPX（3,7-二甲基-1-丙炔基黄嘌呤）拮抗。然而，R-PIA（R-N(6)-(2-苯异丙基)-腺苷；一种特异性腺苷A(1)受体激动剂）诱导了负性变时效应，该效应可被其相应的腺苷A(1)拮抗剂DPCPX（1,3-二丙基-8-环戊基-腺苷）消除。无底物缺氧作为缺血的模拟，导致自发细胞收缩逐渐减少，然后停止。模拟缺血后的复氧过程中，自发节律性收缩活动得以恢复。用R-PIA刺激腺苷A(1)受体可减少缺氧诱导的损伤。这种效应被腺苷A(1)受体拮抗剂DPCPX拮抗。相反，用CGS 21680处理的细胞在复氧后未显示完全恢复。此外，这种效应被DMPX消除，因为细胞在复氧后恢复了正常功能。总之，心肌细胞似乎同时拥有功能性腺苷A(1)和A(2)受体，并且只有腺苷A(1)受体的激活对模拟缺血诱导的心脏细胞损伤具有细胞保护作用。
