Adenosine reduces the reverse mode of the Na+/Ca(2+) exchanger in ferret cardiac fibres.

The aim of this study was to investigate the effects of adenosine on reverse mode Na+/Ca(2+) exchange. In intact ferret cardiac trabeculae, Na+-free contractures were investigated after treating preparations with ryanodine, a sarcoplasmic reticulum Ca(2+) -channel inhibitor, and thapsigargin, a sarcoplasmic reticulum Ca(2+) -pump inhibitor added to suppress the sarcoplasmic reticulum function. The effects of adenosine (50-100 nmol/L), adenosine deaminase (ADA, 0.1-0.5 U/L), the A1 and A2A receptor agonists CCPA (3-100 nmol/L) and CGS 21680 (25-100 nmol/L), and the A1 and A2A receptor antagonists DPCPX (25 nmol/L) and ZM 241385 (25 nmol/L) were tested on Na+-free contractures. The application of adenosine (50-100 nmol/L) had no significant effect on the characteristics of the Na+-free contractures. However, the results show that treatment with ADA (0.3 U/L), adenosine (> or =50 nmol/L) and CCPA, a specific A1 receptor agonist (3-100 nmol/L), all reduced the Na+-free contracture amplitude. In the presence of ADA, the effects of adenosine and CCPA were also reduced by a specific antagonist of A1 receptors (DPCPX, 25 nmol/L). Furthermore, adenosine, ADA, and CCPA did not affect the properties of the contractile apparatus in Triton-skinned fibres. It is therefore proposed that endogenous adenosine reduced the reverse mode of the Na+/Ca(2+) exchanger by acting on A1 receptors present in the sarcolemmal membrane.