Kubista Helmut, Boehm Stefan
Institute of Pharmacology, Centre of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Waehringer Strasse 13a, A-1090 Vienna, Austria.
Pharmacol Ther. 2006 Oct;112(1):213-42. doi: 10.1016/j.pharmthera.2006.04.005. Epub 2006 May 30.
The release of noradrenaline from nerve terminals is modulated by a variety of presynaptic receptors. These receptors belong to one of the following three receptor superfamilies: transmitter-gated ion channels, G protein-coupled receptors (GPCR), and membrane receptors with intracellular enzymatic activities. For representatives of each of these three superfamilies, receptor activation has been reported to cause either an enhancement or a reduction of noradrenaline release. As these receptor classes display greatly diverging structures and functions, a multitude of different molecular mechanisms are involved in the regulation of noradrenaline release via presynaptic receptors. This review gives a short overview of the presynaptic receptors on noradrenergic nerve terminals and summarizes the events involved in vesicle exocytosis in order to finally delineate the most important signaling cascades that mediate the modulation via presynaptic receptors. In addition, the interactions between the various presynaptic receptors are described and the underlying molecular mechanisms are elucidated. Together, these presynaptic signaling mechanisms form a sophisticated network that precisely adapts the amount of noradrenaline being released to a given situation.
神经末梢去甲肾上腺素的释放受多种突触前受体的调节。这些受体属于以下三个受体超家族之一：递质门控离子通道、G蛋白偶联受体（GPCR）和具有细胞内酶活性的膜受体。对于这三个超家族中的每一个家族的代表，据报道受体激活可导致去甲肾上腺素释放增强或减少。由于这些受体类别具有非常不同的结构和功能，通过突触前受体调节去甲肾上腺素释放涉及多种不同的分子机制。本综述简要概述了去甲肾上腺素能神经末梢上的突触前受体，并总结了囊泡胞吐作用中涉及的事件，以便最终描绘出介导通过突触前受体进行调节的最重要信号级联反应。此外，还描述了各种突触前受体之间的相互作用，并阐明了其潜在的分子机制。这些突触前信号机制共同形成了一个复杂的网络，可精确地使释放的去甲肾上腺素量适应特定情况。
