Zaidi Z F, Matthews M R
Department of Human Anatomy, University of Oxford, U.K.
Neuroscience. 1997 Oct;80(3):861-91. doi: 10.1016/s0306-4522(96)00664-1.
Stimulant-induced exocytosis has been demonstrated in sympathetic ganglia of the rat by in vitro incubation of excised ganglia in the presence of tannic acid, which stabilizes vesicle cores after their exocytotic release. Sites of exocytosis were observed along non-synaptic regions of the surfaces of neuron somata and dendrites, including regions of dendrosomatic and dendrodendritic apposition, as well as along the surfaces of nerve terminals About half the exocytoses associated with nerve terminals were parasynaptic or synaptic, and these appeared mostly to arise from the presynaptic terminal, but occasionally from the postsynaptic element. The results demonstrated that the neurons of sympathetic ganglia release materials intraganglionically in response to stimulation, that release from different parts of the neuron is subject to independent regulation, at least via cholinergic receptors, and that release is partly diffuse, potentially mediating autocrine or paracrine effects, and partly targeted toward other neurons, but that the latter mode is not necessarily, and not evidently, synaptic. Specifically, exocytosis from all locations increased significantly during incubation in modified Krebs' solution containing 56 nm potassium. Observation of the effects of cholinergic agonists (nicotine, carbachol, oxotremorine) and antagonists (atropine, AF-DX 116) showed that nicotinic and muscarinic excitation each, independently, increased the incidence of exocytosis from somata and dendrites. Exocytosis from nerve endings was not altered by nicotine, but was enhanced or, at high initial rates of exocytosis, decreased, by muscarinic stimulation. Evidence was obtained for muscarinic auto-inhibition of exocytosis from nerve terminals, occurring under basal incubation conditions, and for a muscarinic excitatory component of somatic exocytosis, elicitable by endogenous acetylcholine. The M2-selective muscarinic antagonist AF-DX 116 was found to modify the exocytotic response of the dendrites to oxotremorine, widening the range of its variation; this effect is consistent with recent evidence for the presence of M2-like muscarinic binding sites, in addition to M1-like binding, upon these dendrites [Ramcharan E. J. and Matthews M. R. (1996) Neuroscience 71, 797-832]. Over all conditions, disproportionately more sites of somatic and dendritic exocytosis were found to be located in regions of dendrosomatic and dendrodendritic apposition than would be expected from the relative extent of the neuronal surface occupied by these relationships. Such mechanisms of intraganglionic release may be expected to contribute to the regulation and integration of the behaviour of the various functionally distinctive populations of neurons in these ganglia, by autocrine, paracrine, and focal, neuroneuronal, routes of action. Similar phenomena of exocytotic soma-dendritic release might prove to subserve integrative neuroneuronal interactions more widely throughout the nervous system.
通过在含有鞣酸的情况下对大鼠离体交感神经节进行体外孵育，已证实在大鼠交感神经节中存在兴奋剂诱导的胞吐作用，鞣酸可在囊泡核心胞吐释放后使其稳定。在神经元胞体和树突表面的非突触区域观察到了胞吐作用的位点，包括树突-胞体和树突-树突毗邻区域，以及神经末梢表面。与神经末梢相关的胞吐作用中，约一半是旁突触或突触性的，这些大多似乎起源于突触前末梢，但偶尔也起源于突触后成分。结果表明，交感神经节的神经元在受到刺激时会在神经节内释放物质，神经元不同部位的释放至少通过胆碱能受体受到独立调节，释放部分是弥散性的，可能介导自分泌或旁分泌作用，部分是针对其他神经元的，但后一种模式不一定是，也不明显是突触性的。具体而言，在含有56纳米钾的改良克雷布斯溶液中孵育期间，所有位置的胞吐作用均显著增加。观察胆碱能激动剂（尼古丁、卡巴胆碱、氧化震颤素）和拮抗剂（阿托品、AF-DX 116）的作用表明，烟碱和毒蕈碱兴奋各自独立地增加了胞体和树突的胞吐发生率。尼古丁不会改变神经末梢的胞吐作用，但毒蕈碱刺激会增强或在胞吐初始速率较高时降低神经末梢的胞吐作用。有证据表明，在基础孵育条件下，毒蕈碱对神经末梢的胞吐作用有自动抑制作用，以及内源性乙酰胆碱可引发胞体胞吐作用的毒蕈碱兴奋成分。发现M2选择性毒蕈碱拮抗剂AF-DX 116可改变树突对氧化震颤素的胞吐反应，扩大其变化范围；这种效应与最近的证据一致，即在这些树突上除了存在M1样结合位点外，还存在M2样毒蕈碱结合位点[Ramcharan E. J.和Matthews M. R.（1996年）《神经科学》71卷，797 - 832页]。在所有条件下，发现胞体和树突胞吐作用的位点在树突-胞体和树突-树突毗邻区域的分布比例，比根据这些关系所占据的神经元表面相对范围预期的要高。这种神经节内释放机制可能通过自分泌、旁分泌以及局部的神经元-神经元作用途径，有助于调节和整合这些神经节中各种功能不同的神经元群体的行为。类似的胞体-树突胞吐释放现象可能更广泛地在整个神经系统中参与整合性的神经元-神经元相互作用。
