Adenosine inhibits collagen and protein synthesis in cardiac fibroblasts: role of A2B receptors

Hypertension. 1998 Apr;31(4):943-8. doi: 10.1161/01.hyp.31.4.943.

Abstract

The objective of this study was to characterize the effects of exogenous and endogenous (cardiac fibroblast-derived) adenosine on [3H]proline and [3H]leucine incorporation, which are reliable markers of collagen and total protein synthesis, respectively, in rat left ventricular cardiac fibroblasts. Growth-arrested confluent cardiac fibroblast monolayers were stimulated with 2.5% fetal calf serum (FCS) in the presence and absence of adenosine, 2-chloroadenosine (stable adenosine analogue), or modulators of adenosine levels including (1) erythro-9-(2-hydroxy-3-nonyl) adenine (adenosine deaminase inhibitor), (2) dipyridamole (adenosine transport blocker), and (3) iodotubericidin (adenosine kinase inhibitor). All agents inhibited in a concentration-dependent fashion FCS-induced [3H]proline and [3H]leucine incorporation. These effects were blocked by KF17837 (selective A2 antagonist) and 1,3-dipropyl-8-(p-sulfophenyl)xanthine (A1/A2 receptor antagonist) but not by 8-cyclopentyl-1,3-dipropylxanthine (selective A1 antagonist), thus excluding the participation of A1 receptors. The lack of effect of CGS21680 (selective A2A agonist) excluded involvement of A2A receptors, thus suggesting a major role for A2B receptors. Comparisons of the inhibitory potencies of N6-cyclopentyladenosine (selective A1 agonist), 5'-N-ethylcarboxamidoadenosine (A1/A2 agonist), and 5'-N-methylcarboxamidoadenosine (A1/A2 agonist) were consistent with that of an A2B receptor subtype mediating the inhibitory effects. We conclude that adenosine inhibits FCS-induced collagen and total protein synthesis in cardiac fibroblasts via activation of A2B receptors. These studies suggest, but do not prove, that endogenous adenosine may protect against cardiac fibrosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Chloroadenosine / pharmacology
  • Adenosine / pharmacology*
  • Adenosine / physiology
  • Animals
  • Cardiovascular Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Division / drug effects
  • Collagen / biosynthesis
  • Collagen / drug effects*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibrosis / metabolism
  • Heart Ventricles / cytology
  • Male
  • Myocardial Infarction / metabolism
  • Protein Biosynthesis
  • Proteins / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2B
  • Receptors, Purinergic P1 / drug effects*
  • Receptors, Purinergic P1 / metabolism

Substances

  • Cardiovascular Agents
  • Proteins
  • Receptor, Adenosine A2B
  • Receptors, Purinergic P1
  • 2-Chloroadenosine
  • Collagen
  • Adenosine