α-Bungarotoxin-sensitive nicotinic receptors indirectly modulate [3H]dopamine release in rat striatal slices via glutamate release
α-Bungarotoxin-sensitive nicotinic receptors indirectly modulate [3H]dopamine release in rat striatal slices via glutamate release
复制标题
DOI：
10.1124/mol.58.2.312
复制
发表时间：
2000-08-01
影响因子：
3.6
通讯作者：
Wonnacott, S
中科院分区：
文献类型：
--
作者：
Kaiser, S;Wonnacott, S
尼古丁激动剂通过作用于多巴胺神经末梢的突触前尼古丁乙酰胆碱受体（nAChRs），诱导纹状体突触体释放多巴胺。α 3 β 2*和α 4 β 2 nAChR亚型（但不包括α 7* nAChR）都有牵连。本研究比较了nachr诱发的纹状体突触体[H-3]多巴胺释放和烟碱激动剂anatoxin-a对切片的影响。在更完整的切片制备中，anatoxin-a诱发[H-3]多巴胺释放的浓度-响应曲线最适合于两个位点模型，给出的EC50值为241 nM和5.1 μ M，而在突触体制备中只观察到高亲和力成分（EC50 = 134 nM）。切片（但不包括突触体）对高浓度anatoxin-a （25 μ M）的反应被嗜离子性谷氨酸受体拮抗剂（犬尿酸，6,7-二硝基喹啉-2,3-二酮）和α 7*选择性nAChR拮抗剂（α -bungarotoxin, α -conotoxin- imi，甲基莱卡乌碱）以非加性方式部分阻断。相比之下，α 3 β 2选择性nAChR拮抗剂α -conotoxin- mii在低（1 μ M）和高（25 μ M）浓度的anatoxin-a刺激下，部分抑制了切片和突触体制剂中[H-3]多巴胺的释放。α -conotoxin- mii的拮抗作用与α - 7*选择性拮抗剂的拮抗作用是叠加的。这些数据支持了纹状体谷氨酸末端的α 7* nachr引发谷氨酸释放的模型，谷氨酸释放反过来作用于多巴胺末端的嗜离子性谷氨酸受体，刺激多巴胺释放。此外，多巴胺末端的非α 7* nachr也刺激多巴胺释放。这些观察结果对纹状体主要输出神经元输入的复杂胆碱能调节具有启示意义。
Nicotinic agonists elicit the release of dopamine from striatal synaptosomes by acting on presynaptic nicotinic acetylcholine receptors (nAChRs) on dopamine nerve terminals. Both alpha 3 beta 2* and alpha 4 beta 2 nAChR subtypes (but not alpha 7* nAChRs) have been implicated. Here, we compared nAChR-evoked [H-3]dopamine release from rat striatal synaptosome and slice preparations by using the nicotinic agonist anatoxin-a. In the more integral slice preparation, the concentration-response curve for anatoxin-a-evoked [H-3]dopamine release was best fitted to a two-site model, giving EC50 values of 241 nM and 5.1 mu M, whereas only the higher-affinity component was observed in synaptosome preparations (EC50 = 134 nM). Responses to a high concentration of anatoxin-a (25 mu M) in slices (but not in synaptosomes) were partially blocked by ionotropic glutamate receptor antagonists (kynurenic acid, 6,7-dinitroquinoxaline-2,3-dione) and by alpha 7*-selective nAChR antagonists (alpha-bungarotoxin, alpha-conotoxin-ImI, methyllycaconitine) in a nonadditive manner. In contrast, the alpha 3 beta 2-selective nAChR antagonist alpha-conotoxin-MII partially inhibited [H-3]dopamine release from both slice and synaptosome preparations, stimulated with both low (1 mu M) and high (25 mu M) concentrations of anatoxin-a. Antagonism by alpha-conotoxin-MII was additive with that of alpha 7*-selective antagonists. These data support a model in which alpha 7* nAChRs on striatal glutamate terminals elicit glutamate release, which in turn acts at ionotropic glutamate receptors on dopamine terminals to stimulate dopamine release. In addition, non-alpha 7* nAChRs on dopamine terminals also stimulate dopamine release. These observations have implications for the complex cholinergic modulation of inputs onto the major efferent neurons of the striatum.