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Methylxanthines and Ryanodine Receptor Channels

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Methylxanthines

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 200))

Abstract

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.

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Notes

  1. 1.

    Botanical sources and bioconversion pathways of methylxanthines are described in detail in Ashihara et al. (2010) and Arnaud (2010), respectively.

  2. 2.

    See Francis et al. (2010) for details on the pharmacological effects of methylxanthines that are mediated by adenosine receptor blockade or phosphodiesterase inhibition.

Abbreviations

Ca 2+cyt :

Cytoplasmic Ca2+

ER:

Endoplasmic reticulum

RyR:

Ryanodine receptor

SR:

Sarcoplasmic reticulum

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Acknowledgements

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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Authors and Affiliations

  1. Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière, UMR-S975, Université Pierre et Marie Curie-Paris 6, Paris, France

    Serge Guerreiro & Patrick P. Michel

  2. U-975, Institut National de la Santé et de la Recherche Médicale, Paris, France

    Serge Guerreiro & Patrick P. Michel

  3. UMR 7225, Centre National de la Recherche Scientifique, Paris, France

    Serge Guerreiro & Patrick P. Michel

  4. Institut de Recherche Pierre Fabre, Castres, France

    Marc Marien & Patrick P. Michel

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  1. Serge Guerreiro
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  2. Marc Marien
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  3. Patrick P. Michel
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Correspondence to Patrick P. Michel .

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Guerreiro, S., Marien, M., Michel, P.P. (2011). Methylxanthines and Ryanodine Receptor Channels. In: Methylxanthines. Handbook of Experimental Pharmacology, vol 200. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13443-2_5

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