Feil Robert, Hofmann Franz, Kleppisch Thomas
Institut für Pharmakologie und Toxikologie, Technische Universität München, München, Germany.
Rev Neurosci. 2005;16(1):23-41. doi: 10.1515/revneuro.2005.16.1.23.
The second messenger cyclic guanosine-3',5'-monophosphate (cGMP) mediates many effects of nitric oxide in the nervous system. cGMP may act through various intracellular receptors, among them a family of serine/threonine kinases, the cGMP-dependent protein kinases (cGKs). Hitherto, three mammalian cGKs have been identified: cGKIalpha, cGKIbeta and cGKII. Discrete functions of cGKI and cGKII are determined by their distinct expression patterns and targeting to specific substrates. This review provides an overview about the expression and functions of cGKs in the nervous system. Main emphasis is put on the discussion of phenotypes observed in cGK-deficient mouse models that lack cGKI and/or cGKII globally or selectively in brain regions of interest. Recent data demonstrate important functions of cGKI in (1) the development and sensitization of nociceptive neurons, and (2) synaptic plasticity and learning. There is also evidence suggesting that cGKII in the suprachiasmatic nucleus of the hypothalamus is involved in the regulation of circadian rhythmicity. Thus, cGKs serve key functions in the transduction of cGMP signals into cellular responses in distinct regions of the nervous system.-
第二信使环磷酸鸟苷（cGMP）介导一氧化氮在神经系统中的多种作用。cGMP可能通过多种细胞内受体发挥作用，其中包括丝氨酸/苏氨酸激酶家族，即cGMP依赖性蛋白激酶（cGKs）。迄今为止，已鉴定出三种哺乳动物cGKs：cGKIα、cGKIβ和cGKII。cGKI和cGKII的不同功能由其独特的表达模式和对特定底物的靶向作用决定。本综述概述了cGKs在神经系统中的表达和功能。主要重点讨论了在cGK缺陷小鼠模型中观察到的表型，这些模型在感兴趣的脑区整体或选择性地缺乏cGKI和/或cGKII。最新数据表明cGKI在（1）伤害性神经元的发育和敏化，以及（2）突触可塑性和学习中具有重要功能。也有证据表明，下丘脑视交叉上核中的cGKII参与昼夜节律的调节。因此，cGKs在将cGMP信号转化为神经系统不同区域的细胞反应中发挥关键作用。
