TY - JOUR
T1 - Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts
AU - Epperson, Sara A.
AU - Brunton, Laurence L.
AU - Ramirez-Sanchez, Israel
AU - Villarreal, Francisco
PY - 2009/5
Y1 - 2009/5
N2 - The ability of adenosine (ADO) to inhibit proliferation and protein synthesis (in particular, collagen synthesis) in cardiac fibroblasts (CF) 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 A 3R) are present in rat CF, with a greater prevalence of A2 receptor subtypes. No coupling of AR to the Gq-phospholipase C signaling pathway or to mobilization of calcium is measurable. Studies using subtype specific agents imply that the A2aR and A2bR couple to Gs-adenylyl cyclase and A1R couple weakly to Gi-adenylyl cyclase. 2-Chloroadenosine, 5'-N- ethylcarboxamidoadensoine, and other agents that elevate cellular cAMP stimulate extracellular signal-regulated kinase 1/2 activity in a pertussis toxin-insensitive manner. We conclude that a combination of cAMP-dependent signals generated via A2a and A2b receptors likely mediate ADO signaling in adult rat CF.
AB - The ability of adenosine (ADO) to inhibit proliferation and protein synthesis (in particular, collagen synthesis) in cardiac fibroblasts (CF) 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 A 3R) are present in rat CF, with a greater prevalence of A2 receptor subtypes. No coupling of AR to the Gq-phospholipase C signaling pathway or to mobilization of calcium is measurable. Studies using subtype specific agents imply that the A2aR and A2bR couple to Gs-adenylyl cyclase and A1R couple weakly to Gi-adenylyl cyclase. 2-Chloroadenosine, 5'-N- ethylcarboxamidoadensoine, and other agents that elevate cellular cAMP stimulate extracellular signal-regulated kinase 1/2 activity in a pertussis toxin-insensitive manner. We conclude that a combination of cAMP-dependent signals generated via A2a and A2b receptors likely mediate ADO signaling in adult rat CF.
KW - Extracellular matrix
KW - G protein-linked receptors
KW - Myocardial fibrosis
UR - http://www.scopus.com/inward/record.url?scp=66149095641&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00290.2008
DO - 10.1152/ajpcell.00290.2008
M3 - Artículo
C2 - 19244482
SN - 0363-6143
VL - 296
SP - C1171-C1177
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 5
ER -