Inhibition of caffeine-induced Ca2+ release by adenosine in mammalian skinned slow- and fast-twitch fibres

The present study performed on chemically skinned skeletal fibres was desig ned to compare the effects of adenosine on the Ca2+ sensitivity of contract ile proteins and on caffeine-induced Ca2+ release in rat slow(soleus) and f ast-twitch (edl) muscles. The tension-pCa relationships were obtained by exposing triton X-100 (1% v/ v) skinned fibres sequentially to solutions of decreasing pCa in the presen ce or in absence of adenosine. Then. changes in caffeine contracture due to adenosine were recorded on saponin (50 mug/ml) skinned fibres. The results show that the sensitivity to Ca2+ of contractile proteins in th e presence of different concentrations of caffeine was not significantly mo dified by adenosine. However, it was proposed that adenosine (0.1-2 mM) red uced the Ca2+ released by caffeine (0.1-10 mM) from the sarcoplasmic reticu lum in slow- and fast-twitch fibres and that the soleus was more sensitive to adenosine than edl muscle. The effects of specific A(2a) and A(1) agonis ts and antagonists were also tested on caffeine contractures. It was found that the A(1) antagonist reduced adenosine effect on caffeine response. The n it is proposed that adenosine modulates the sarcoplasmic reticulum Ca2+ r elease by a direct effect on the RyR1 receptors and/or by an indirect effec t mediated by A(1) receptors located at the sarcoplasmic level.