Abstract 15987: Activation of NADPH Oxidase by Adenosine in Isolated Heart and Coronary Artery Smooth Muscle Cells Involves Phosphorylation of ERK 1/2 And P47-phox: Role of A1 and A3 Adenosine Receptors
Although reactive oxygen species (ROS) have been linked to adenosine responses in different tissues, little is known about the involvement of ROS in adenosine-induced CF responses. We hypothesized that ROS generated through NADPH oxidase (Nox) is involved in adenosine-induced coronary flow (CF) responses. We examined the contribution of A1 and A3 adenosine receptors (ARs) in adenosine-induced superoxide generation and CF responses using isolated hearts from wild type (WT; C57/BL6), A1AR knockout (A1KO), A3AR KO (A3KO) and A1 and A3AR double KO (A1/A3DKO) mice. Adenosine (10-8 -10-5.5 M) increased CF in WT and the three KO mice isolated hearts. The Nox inhibitors apocynin (10-5 M) and gp91 ds-tat (10-6 M) or the SOD and catalase mimicking EUK134 (50 µM) decreased the adenosine enhanced CF, with no differences between the WT and all three KO mice isolated hearts. In addition, adenosine increased phosphorylation of p47-phox subunit and ERK 1/2 without changing protein expression of Nox isoforms 1, 2 and 4 in WT mice isolated hearts. Moreover, adenosine increased intracellular superoxide production by Nox in coronary artery smooth muscle cells (CASMCs) from mouse and human, but not in human coronary artery endothelial cells (CAECs). In conclusion, adenosine-induced increase in CF of isolated mouse heart involves superoxide generated from Nox, possibly through ERK 1/2 phosphorylation with subsequent p47-phox subunit phosphorylation. This interaction between adenosine and ROS/Nox occurs in CASMCs, but not CAECs, and involves neither A1 nor A3 ARs, but possibly A2AAR and/or A2BAR activation.
- © 2012 by American Heart Association, Inc.