Cardiac myocyte adenosine A_2areceptor activation fails to alter cAMP or contractility: role of receptor localization

Abstract

Adenosine A2a receptors are found in coronary vascular tissue although, their presence in myocardium is subject to investigation. Although there have been numerous studies on adenosine A2a receptor agonist effects on contractility and cAMP levels in ventricular myocytes, these have yielded conflicting results. Negative pharmacological studies have even led to the conclusion that A2a receptors are not present in cardiac myocytes. The purpose of this study was to determine whether A2a receptors are expressed in rat ventricular myocytes and what physiological effects are mediated via activation of these receptors. Western blot analysis with a polyclonal antibody raised against a peptide sequence specific to the carboxy terminus of the A2a receptor revealed the presence of a band at approximately 45 kDa. However, the immunoreactivity was located in the nonmembrane fraction of the cell lysate. The membrane fraction only exhibited an immunoreactive band > or = 50 kDa. Treatment of isolated myocytes with the adenosine A2a agonist 2-[4-[(2-carboxyethyl)-phenyl]ethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680) exerted no effects on cAMP levels or myocyte twitch amplitude. These results indicate that although rat ventricular myocytes appear to express adenosine A2a receptors, stimulation with an A2a agonist exerts no functional effects, possibly because of the subcellular localization of the A2a receptor.

The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium

“…It is thought that both of these receptors exert their protection via direct effects on the cardiac myocytes, although to date there remains no definitive evidence that A 3 receptors are expressed in adult ventricular myocytes. Although there is evidence that adenosine A 2a receptors are expressed in ventricular cardiomyocytes (10,20), the results of a very limited number of studies indicate that the administration of A 2a receptor agonists before ischemia does not induce cardioprotection (1, 13, 32, 33). The results of the present in vivo study confirm the inability of a selective A 2a receptor agonist (CGS-21680) to reduce infarct size when administered before ischemia.…”

“…Additional reports that A 2a receptor postconditioning can be induced in isolated perfused heart preparations (35, 36) suggest that direct myocardial effects may be involved. It has also been reported that rat, porcine, and human ventricular myocytes express A 2a receptors (10,20), raising the possibility that A 2a receptor activation may modulate the cardiomyocyte response to ischemia-reperfusion.Although the administration of A 2a agonists before ischemia does not reduce infarct size, there are an increasing number of reports of interactions between A 1 and A 2a receptors. Interactions between adenosine A 1 and A 2a receptors have been reported in rat striatum and hippocampus (6, 8, 16 -18, 23).…”

“…Additional reports that A 2a receptor postconditioning can be induced in isolated perfused heart preparations (35,36) suggest that direct myocardial effects may be involved. It has also been reported that rat, porcine, and human ventricular myocytes express A 2a receptors (10,20), raising the possibility that A 2a receptor activation may modulate the cardiomyocyte response to ischemia-reperfusion.…”

Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

“…Hence, A 2A R activation could not lead to any change in I h . A second possibility that may be pertinent to our results is the absence of functional A 2A R or A 3 R proteins in cardiac myocytes [10,30] . These two lines of evidence completely rule out the involvement of A 2A R and A 3 R in the present study.…”

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

“…A2AAR can be found in the brain [17], ventricular myocytes [18], endothelial cells [19], carotid body [20], and immune cells [20,21], among other tissues. With such a wide distribution, A2AAR has been linked to several processes, including protection against ischemia-reperfusion injury [22], coronary vasodilatation [23], sleep regulation [24], control of inflammation [21], citing but a few biological events related to such receptor.…”