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Am J Physiol Cell Physiol (February 25, 2009). doi:10.1152/ajpcell.00290.2008
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Submitted on June 2, 2008
Revised on February 12, 2009
Accepted on February 13, 2009

Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts

Sara Ann Epperson1, Laurence L Brunton2, Israel Ramirez-Sanchez3, and Francisco J. Villarreal3*

1 UC San Diego
2 M-0636
3 University of California at San Diego

* To whom correspondence should be addressed. E-mail: fvillarr{at}ucsd.edu.

The ability of adenosine (ADO) to inhibit cardiac fibroblast (CF) proliferation and protein synthesis (in particular, collagen synthesis) may ameliorate adverse cardiac remodeling and fibrosis seen in heart failure patients. However, little is known about the signaling pathways that ADO may modulate in CF to alter cell phenotype. Accordingly, this study was designed to identify ADO receptors (AR) and the signaling pathways linked to them in primary cultures of adult rat CF. Quantitative RT-PCR data indicate that the mRNAs for all four known ARs (A1R, A2aR, A2bR, and A3R) are present in rat CF, with a greater prevalence of A2 receptor subtypes. No coupling of AR to the Gq/phospholipase C signaling pathway was identified. Studies using subtype specific agents imply that the A2aR and A2bR couple to Gs/adenylyl cyclase and A1R couple weakly to Gi/adenylyl cyclase. We conclude that a combination of cAMP-dependent signals generated via A2a and A2b receptors likely mediate ADO signaling in adult rat CF.




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F. Villarreal, S. A. Epperson, I. Ramirez-Sanchez, K. G. Yamazaki, and L. L. Brunton
Regulation of cardiac fibroblast collagen synthesis by adenosine: roles for Epac and PI3K
Am J Physiol Cell Physiol, May 1, 2009; 296(5): C1178 - C1184.
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