Indirect modulation by α7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices:: Interaction with glutamate and GABA systems and effect of nicotine withdrawal
Indirect modulation by α7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices:: Interaction with glutamate and GABA systems and effect of nicotine withdrawal
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DOI：
10.1124/mol.105.018184
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Wonnacott, S
中科院分区：
文献类型：
--
作者：
Barik, J;Wonnacott, S
烟碱型乙酰胆碱受体（nAChRs）可以调节递质的释放。纹状体[H-3]多巴胺（[H-3]DA）的释放受突触前多巴胺能末梢上的nAChR和邻近多巴胺能传入纤维上的α 7 nAChR的调节。在这里，我们探讨了α 7 nAChR在调节大鼠海马脑片[H-3]去甲肾上腺素（[H-3] NA）释放中的作用。烟碱激动剂类毒素-a（AnTx）诱发双相[H-3] NA释放（EC 50 = 1.2 μ M），其不受α-芋螺毒素-MII或二氢-β-赤藓定碱（分别为α 3/α 6 β 2* 和β 2* nAChR的拮抗剂）的影响。相反，AnTx诱发的纹状体[H-3] DA释放是双相的（EC 50 = 138.9 nM; 7.1 μ M），并被这些拮抗剂阻断。在高AnTx浓度（25 μ M）下，α 7 nAChR拮抗剂（methyllycaconitine，α-芋螺毒素-Iml）和谷氨酸受体（GluR）拮抗剂[犬尿烯酸，6，7-二硝基喹喔啉-2，3-二酮（DNQX）]部分抑制[H-3] NA释放。α 7 nAChR选择性激动剂胆碱诱发3 H] NA释放（E-max = AnTx的33%），其被GluR拮抗剂阻断，支持α 7 nAChR触发谷氨酸释放随后刺激[H-3] NA释放的模型。GABA（A）受体拮抗剂荷包牡丹碱可部分阻断胆碱诱发的[H-3] NA释放，荷包牡丹碱和DNQX合用可完全阻断这种反应。这些发现支持GABA能神经元上的α 7 nAChR可以促进GABA释放，这反过来又导致[H-3] NA释放，可能是通过去抑制。为了研究长期尼古丁暴露对该模型的影响，将大鼠暴露于尼古丁（4 mg/kg/天）14天，伴有或不伴有3天或7天停药。戒断3天后，α 7 nAChR反应选择性和短暂上调。这种功能性上调可能有助于尼古丁的戒断作用。
Nicotinic acetylcholine receptors (nAChRs) can modulate transmitter release. Striatal [H-3] dopamine ([H-3]DA) release is regulated by presynaptic nAChR on dopaminergic terminals and alpha 7 nAChR on neighboring glutamatergic afferents. Here, we explored the role of alpha 7 nAChR in the modulation of [H-3] noradrenaline ([H-3] NA) release from rat hippocampal slices. The nicotinic agonist anatoxin-a ( AnTx) evoked monophasic [H-3] NA release (EC50 = 1.2 mu M) that was unaffected by alpha-conotoxin-MII or dihydro-beta-erythroidine, antagonists of alpha 3/alpha 6 beta 2* and beta 2* nAChR, respectively. In contrast AnTx-evoked striatal [H-3] DA release was biphasic (EC50 = 138.9 nM; 7.1 mu M) and blocked by these antagonists. At a high AnTx concentration ( 25 mu M), alpha 7 nAChR antagonists ( methyllycaconitine, alpha-conotoxin-Iml) and glutamate receptor (GluR) antagonists [ kynurenic acid, 6,7-dinitroquinoxaline- 2,3-dione ( DNQX)] partially inhibited [H-3] NA release. The alpha 7 nAChR-selective agonist choline evoked 3H] NA release ( E-max = 33% of that of AnTx) that was blocked by GluR antagonists, supporting a model in which alpha 7 nAChRs trigger glutamate release that subsequently stimulates [H-3] NA release. A GABAergic component was also revealed: choline-evoked [H-3] NA release was partially blocked by the GABA(A) receptor antagonist bicuculline, and coapplication of bicuculline and DNQX fully abolished this response. These findings support alpha 7 nAChR on GABAergic neurons that can promote GABA release which, in turn, leads to [H-3] NA release, probably by disinhibition. To investigate the impact of long-term nicotine exposure on this model, rats were exposed for 14 days to nicotine ( 4 mg/kg/day) with or without 3 or 7 days of withdrawal. alpha 7 nAChR responses were selectively and transiently up-regulated after 3 days of withdrawal. This functional up-regulation could contribute to the withdrawal effects of nicotine.