A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction.

Article Details

Citation

Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM

A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction.

Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16.

PubMed ID
17438146 [ View in PubMed
]
Abstract

BACKGROUND: It is well known that adenosine levels are increased during ischemia and protect the heart during ischemia/reperfusion. However, less is known about the role of adenosine-adenosine receptor (AR) pathways in hearts with left ventricular dilation and dysfunction. Therefore, we assessed adenosine levels and selective AR expression in transgenic mice with left ventricular systolic dysfunction secondary to overexpression of tumor necrosis factor-alpha (TNF 1.6). METHODS AND RESULTS: Cardiac adenosine levels were reduced by 70% at 3 and 6 weeks of age in TNF 1.6 mice. This change was accompanied by a 4-fold increase in the levels of A1-AR and a 50% reduction in the levels of A2A-AR. That the increase in A1-AR density was of physiological significance was shown by the fact that chronotropic responsiveness to the A1-AR selective agonist 2-chloro-N6-cyclopentanyladenosine was enhanced in the TNF 1.6 mice. Similar changes in adenosine levels were found in 2 other models of heart failure, mice overexpressing calsequestrin and mice after chronic pressure overload, suggesting that the changes in adenosine-AR signaling were secondary to myocardial dysfunction rather than to TNF overexpression. CONCLUSIONS: Cardiac dysfunction secondary to the overexpression of TNF is associated with marked alterations in myocardial levels of adenosine and ARs. Modulation of the myocardial adenosine system and its signaling pathways may be a novel therapeutic target in patients with heart failure.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AdenosineAdenosine receptor A1ProteinHumans
Yes
Agonist
Details
AdenosineAdenosine receptor A2aProteinHumans
Yes
Agonist
Details
AdenosineAdenosine receptor A2bProteinHumans
Yes
Agonist
Details
AdenosineAdenosine receptor A3ProteinHumans
Yes
Agonist
Details