Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts

• Published in: American Journal of Physiology: Cell Physiology 2009-05, Vol.296 (5), p.C1171-C1177
• Main Authors: Epperson, Sara A, Brunton, Laurence L, Ramirez-Sanchez, Israel, Villarreal, Francisco
• Format: Article
• Language: English
• Subjects: Adenosine; Adrenergic Agonists - pharmacology; Adrenergic Antagonists - pharmacology; Animals; Biochemistry; Cells, Cultured; Collagen - biosynthesis; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Extracellular Matrix - metabolism; Extracellular Matrix, Cell Interactions; Fibroblasts - cytology; Fibroblasts - metabolism; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; Heart; Heart failure; Male; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Myocardium - cytology; Myocardium - metabolism; Phosphoinositide Phospholipase C - metabolism; Protein synthesis; Proteins; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2B - genetics; Receptor, Adenosine A2B - metabolism; Receptor, Adenosine A3 - genetics; Receptor, Adenosine A3 - metabolism; Receptors, Adrenergic, alpha-1 - genetics; Receptors, Adrenergic, alpha-1 - metabolism; Receptors, Adrenergic, alpha-2 - genetics; Receptors, Adrenergic, alpha-2 - metabolism; Receptors, Purinergic P1 - genetics; Receptors, Purinergic P1 - metabolism; RNA, Messenger - metabolism; Rodents; Second Messenger Systems - physiology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00290.2008

Departments of 1 Medicine and 2 Pharmacology and 3 Biomedical Sciences PhD Program, University of California, San Diego, School of Medicine, La Jolla, California Submitted 2 June 2008 ; accepted in final form 13 February 2009 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 (A 1 R, A 2a R, A 2b R, and A 3 R) are present in rat CF, with a greater prevalence of A 2 receptor subtypes. No coupling of AR to the G q -phospholipase C signaling pathway or to mobilization of calcium is measurable. Studies using subtype specific agents imply that the A 2a R and A 2b R couple to G s -adenylyl cyclase and A 1 R couple weakly to G i -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 A 2a and A 2b receptors likely mediate ADO signaling in adult rat CF. G protein-linked receptors;extracellular matrix; myocardial fibrosis Address for reprint requests and other correspondence: F. Villarreal, 9500 Gilman Dr., 0613J, BSB 4028, La Jolla, CA 92093 (e-mail: fvillarr{at}ucsd.edu )