Methylxanthines and Ryanodine Receptor Channels
Methylxanthines of either natural or synthetic origin have a number of interesting pharmacological features. Proposed mechanisms of methylxanthine-induced pharmacological effects include competitive antagonism of G-coupled adenosine A1 and A2A receptors and inhibition of phosphodiesterases. A number of studies have indicated that methylxanthines also exert effects through alternative mechanisms, in particular via activation of sarcoplasmic reticulum or endoplasmic reticulum ryanodine receptor (RyR) channels. More specifically, RyR channel activation by methylxanthines was reported (1) to stimulate the process of excitation coupling in muscle cells, (2) to augment the excitability of neurons and thus their capacity to release neurotransmitters, and also (3) to improve their survival. Here, we address the mechanisms by which methylxanthines control RyR activation and we consider the pharmacological consequences of this activation, in muscle and neuronal cells.
KeywordsCalcium Methylxanthines Muscle cell contraction Neuroprotection Neurotransmitter release Ryanodine receptors
The work by the authors mentioned in this paper received support from Institut de Recherche Pierre Fabre. We gratefully acknowledge support from Institut National de la Santé et de la Recherche Médicale (INSERM) and Université Pierre et Marie Curie-Paris 6.
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