Adenosine affects the release of Ca 2+ from the sarcoplasmic reticulum via A 2A receptors in ferret skinned cardiac fibres

In this study, it was shown that adenosine potentiates caffeine‐induced Ca 2+ release. It was then proposed that the enhancement of the caffeine‐induced Ca 2+ release might occur by a direct effect on the ryanodine Ca 2+ release channel or on other Ca 2+ regulation mechanisms. Furthermore, A 2A receptors may be functional on the ferret cardiac sarcoplasmic reticulum. Using chemically skinned fibres, experiments were conducted on ferret cardiac muscle to find out whether adenosine and the A 1 and A 2A adenosine receptor agonists (CCPA and CGS 21680) and antagonists (DPCPX and ZM 241385) affected caffeine‐induced Ca 2+ release and the Ca 2+ sensitivity of contractile proteins. Changes in the caffeine‐induced contracture brought about by adenosine and by adenosine‐receptor agonists and antagonists were recorded in saponin‐skinned fibres (50 μg ml −1 ). Tension–pCa relationships were then obtained by exposing Triton X‐100‐skinned fibres (1% v/v) sequentially to solutions of decreasing pCa. Adenosine (1–100 n m ) and the specific A 2A receptor agonist CGS 21680 (1–50 n m ) produced a concentration‐dependant potentiation of the caffeine‐induced Ca 2+ release from saponin‐skinned fibres. The data plotted versus adenosine and CGS 21680 concentrations displayed sigmoid relationships (Hill relationship), with potentiation of Ca 2+ release by 22.2 ± 1.6 ( n = 6) and 10.9 ± 0.4% ( n = 6) , respectively. In addition, the potentiation of caffeine‐induced Ca 2+ release by adenosine (50 n m ; 15.3 ± 1.0%; n = 6) and by CGS 21680 (50 n m ; 11.2 ± 0.4%; n = 6) was reduced by the specific A 2A receptor antagonist ZM 241385 (50 n m ) to 8.0 ± 1.4 ( n = 4) and 5.4 ± 1.2% ( n = 4) , respectively. The A 1 receptor agonist CCPA (1–50 n m ) and antagonist DPCPX (50 n m ) had no significant effects on caffeine responses. In Triton X‐100‐skinned fibres, the maximal Ca 2+ ‐activated tension of the contractile proteins (41.3 ± 4.1 mN mm −2 ; n = 8) , the Hill coefficient ( n H = 2.2 ± 0.1; n = 8) and the pCa 50 (6.15 ± 0.05; n = 8) were not significantly modified by adenosine (100 n m ) or by CGS 21680 (50 n m ).