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 designed to compare the effects of adenosine on the Ca2+ sensitivity of contractile proteins and on caffeine-induced Ca2+ release in rat slow- (soleus) and fast-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 presence or in absence of adenosine. Then, changes in caffeine contracture due to adenosine were recorded on saponin (50 microg/ml) skinned fibres. The results show that the sensitivity to Ca2+ of contractile proteins in the presence of different concentrations of caffeine was not significantly modified by adenosine. However, it was proposed that adenosine (0.1-2 mM) reduced the Ca2+ released by caffeine (0.1-10 mM) from the sarcoplasmic reticulum in slow- and fast-twitch fibres and that the soleus was more sensitive to adenosine than edl muscle. The effects of specific A2a and A1 agonists and antagonists were also tested on caffeine contractures. It was found that the A1 antagonist reduced adenosine effect on caffeine response. Then it is proposed that adenosine modulates the sarcoplasmic reticulum Ca2+ release by a direct effect on the RyR1 receptors and/or by an indirect effect mediated by A1 receptors located at the sarcoplasmic level.
Hleihel
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Laboratoire de Physiologie Générale, Centre National de la Recherche Scientifique CNRS UMR 6018, Faculté des Sciences et Techniques, 2 rue de la Houssinière, 44322 Nantes cedex 03, France. Claude.Leoty@svt.univ-nantes.fr
Talon
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Huchet-Cadiou
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Léoty
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D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D014665:Vasodilator Agents; D002110:Caffeine; D000241:Adenosine; D002118:Calcium