Bloom F E
Fed Proc. 1979 Jul;38(8):2203-7.
A wide array of interdisciplinary experiments have served to strengthen the general premise that some central synaptic effects of neurotransmitters may be mediated by cyclic nucleotides. Specific instances of such second messenger mediation are most strongly supported for certain noradrenergic connections of the locus coeruleus (LC) and for dopaminergic connections within the caudate nucleus. In these sites catecholamines selectively activate intraneuronal cyclic AMP synthesis, and exogenously applied cyclic AMP closely mimics the biophysical actions of the catecholamine on target neurons. In cerebellar cortex, iontophoresis of norepinephrine, stimulation of LC, or iontophoresis of cyclic AMP lead to hyperpolarization and increased membrane resistance. Although overtly inhibitory when examined in isolation, the effects of the LC system coupled to adenylate cyclase can initiate a holistic set of target cell responses which can enhance or "enable" the actions of other synaptic inputs to the target cells. Electrophysiologic and immunocytochemical evidence suggests that this heterosynaptic interaction may arise from phosphorylation of the synaptic membrane substrate of cyclic AMP-dependent protein kinase, or Protein 1.
大量的跨学科实验有助于强化这样一个总体前提，即神经递质的某些中枢突触效应可能由环核苷酸介导。这种第二信使介导的具体实例在蓝斑（LC）的某些去甲肾上腺素能连接以及尾状核内的多巴胺能连接中得到了最有力的支持。在这些部位，儿茶酚胺选择性地激活神经元内的环磷酸腺苷（cAMP）合成，而外源性应用的cAMP紧密模拟儿茶酚胺对靶神经元的生物物理作用。在小脑皮质中，去甲肾上腺素的离子电渗法、LC的刺激或cAMP的离子电渗法会导致超极化和膜电阻增加。尽管单独检查时明显具有抑制作用，但与腺苷酸环化酶偶联的LC系统的效应可以引发一组整体的靶细胞反应，这些反应可以增强或“启用”其他突触输入对靶细胞的作用。电生理学和免疫细胞化学证据表明，这种异突触相互作用可能源于环磷酸腺苷依赖性蛋白激酶或蛋白1的突触膜底物的磷酸化。
