Abstract
Adenosine plays a role in regulating the contractile function of the heart. This includes a positive ionotropic action via the adenosine A~2A~ receptor (A~2A~R) and an inhibition of β~1~‐adrenergic receptor‐induced ionotropy (antiadrenergic action) via the adenosine A~1~ receptor (A~1~R). Phosphatase activity has also been shown to influence contractile function by affecting the level of protein phosphorylation. Protein phosphatase 2A (PP2A) plays a significant role in mediating the A~1~R antiadrenergic effect. The purpose of this study was to investigate the effects of A~2A~R and A~1~R on the activities of PP2A in hearts obtained from wild‐type (WT) and A~2A~R knockout (A~2A~R‐KO) mice. PP2A activities were examined in myocardial particulate and cytoplasmic extract fractions. Treatment of wild‐type hearts with the A~1~R agonist CCPA increased the total PP2A activity and increased the particulate:cytoplasmic PP2A activity ratio. Treatment with the A~2A~R agonist CGS‐21680 (CGS) decreased the total PP2A activity and decreased the particulate:cytoplasmic PP2A activity ratio. This indicated a movement of PP2A activity between cell fractions. The effect of CCPA was inhibited by CGS. In A~2A~R‐KO hearts the response to A~1~R activation was markedly enhanced whereas the response to A~2A~R activation was absent. These data show that A~2A~R and A~1~R regulate PP2A activity, thus suggesting an important mechanism for modulating myocardial contractility. J. Cell. Physiol. 216: 83–90, 2008. © 2008 Wiley‐Liss, Inc.