Guerreiro Serge, Marien Marc, Michel Patrick P
Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, Université Pierre et Marie Curie-Paris 6, Paris, France.
Handb Exp Pharmacol. 2011(200):135-50. doi: 10.1007/978-3-642-13443-2_5.
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 A(1) and A(2A) 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.
天然或合成来源的甲基黄嘌呤具有许多有趣的药理学特性。甲基黄嘌呤诱导药理作用的机制包括对G偶联腺苷A(1)和A(2A)受体的竞争性拮抗以及对磷酸二酯酶的抑制。多项研究表明，甲基黄嘌呤还通过其他机制发挥作用，特别是通过激活肌浆网或内质网兰尼碱受体（RyR）通道。更具体地说，据报道甲基黄嘌呤激活RyR通道（1）可刺激肌肉细胞中的兴奋偶联过程，（2）增强神经元的兴奋性，从而提高其释放神经递质的能力，以及（3）改善其存活率。在此，我们探讨甲基黄嘌呤控制RyR激活的机制，并考虑这种激活在肌肉和神经元细胞中的药理学后果。
