Adenosine A1 and A2A receptor regulation of protein phosphatase 2A in the murine heart

Adenosine plays a role in regulating the contractile function of the heart. This includes a positive ionotropic action via the adenosine A2A receptor (A2AR) and an inhibition of β1‐adrenergic receptor‐induced ionotropy (antiadrenergic action) via the adenosine A1 receptor (A1R). Phosphatase activity...

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Bibliographic Details
Published in:Journal of cellular physiology 2008-07, Vol.216 (1), p.83-90
Main Authors: Tikh, Eugene I., Fenton, Richard A., Chen, Jiang-Fan, Schwarzschild, Michael A., Dobson Jr, James G.
Format: Article
Language:English
Subjects:
Adenosine - analogs & derivatives
Adenosine - metabolism
Adenosine A1 Receptor Agonists
Adenosine A2 Receptor Agonists
Animals
Enzyme Activation
Heart - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Contraction - physiology
Myocardium - cytology
Myocardium - metabolism
Phenethylamines - metabolism
Protein Phosphatase 2 - genetics
Protein Phosphatase 2 - metabolism
Receptor, Adenosine A1 - genetics
Receptor, Adenosine A1 - metabolism
Receptor, Adenosine A2A - genetics
Receptor, Adenosine A2A - metabolism
Tyrosine - metabolism
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Summary:Adenosine plays a role in regulating the contractile function of the heart. This includes a positive ionotropic action via the adenosine A2A receptor (A2AR) and an inhibition of β1‐adrenergic receptor‐induced ionotropy (antiadrenergic action) via the adenosine A1 receptor (A1R). 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 A1R antiadrenergic effect. The purpose of this study was to investigate the effects of A2AR and A1R on the activities of PP2A in hearts obtained from wild‐type (WT) and A2AR knockout (A2AR‐KO) mice. PP2A activities were examined in myocardial particulate and cytoplasmic extract fractions. Treatment of wild‐type hearts with the A1R agonist CCPA increased the total PP2A activity and increased the particulate:cytoplasmic PP2A activity ratio. Treatment with the A2AR 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 A2AR‐KO hearts the response to A1R activation was markedly enhanced whereas the response to A2AR activation was absent. These data show that A2AR and A1R regulate PP2A activity, thus suggesting an important mechanism for modulating myocardial contractility. J. Cell. Physiol. 216: 83–90, 2008. © 2008 Wiley‐Liss, Inc.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.21375