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

Hypertension
R K DubeyE K Jackson

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 ...Continue Reading

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