title: Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, La Jolla, CA, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Epperson
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Brunton
authors.forename: Israel
authors.initials: I
authors.lastname: Ramirez-Sanchez
authors.forename: Francisco
authors.initials: F
authors.lastname: Villarreal
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology*
chemical_list: C547770:Adra2a protein, rat; D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D012333:RNA, Messenger; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D018047:Receptors, Purinergic P1; D003094:Collagen; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054801:Phosphoinositide Phospholipase C; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11