Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts

Autor: Francisco Villarreal, Laurence L. Brunton, Sara Epperson, Israel Ramirez-Sanchez
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
medicine.medical_specialty
Adrenergic Antagonists
Physiology
Extracellular Matrix
Cell Interactions

Biology
GTP-Binding Protein alpha Subunits
Gi-Go

Receptor
Adenosine A2B

Second Messenger Systems
Rats
Sprague-Dawley

Phosphoinositide Phospholipase C
Fibrosis
Receptors
Adrenergic
alpha-2

Internal medicine
Receptors
Adrenergic
alpha-1

medicine
Cyclic AMP
Animals
RNA
Messenger

Receptor
Cells
Cultured

G protein-coupled receptor
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Myocardium
Receptor
Adenosine A3

Receptors
Purinergic P1

Cell Biology
Fibroblasts
medicine.disease
Adenosine
Adenosine receptor
Adrenergic Agonists
Cyclic AMP-Dependent Protein Kinases
Cell biology
Extracellular Matrix
Rats
Endocrinology
Second messenger system
GTP-Binding Protein alpha Subunits
Gq-G11

Myocardial fibrosis
Collagen
Signal transduction
medicine.drug
Popis: 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 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 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.
Databáze: OpenAIRE