Release of [3H]‐noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [3H]‐dopamine release
Release of [3H]‐noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [3H]‐dopamine release
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尼古丁从大鼠海马突触体释放[3H]-去甲肾上腺素：纹状体[3H]-多巴胺释放中不同烟碱受体亚型的介导
DOI：
--
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发表时间：
1996
影响因子：
7.3
通讯作者：
M. Reuben
中科院分区：
文献类型：
--
作者：
P. Clarke;M. Reuben
1本实验的目的是以纹状体[~3H]-多巴胺释放为对照，研究尼古丁诱导的大鼠海马突触体内尼古丁诱导的去甲肾上腺素([~3H]-NA)释放。2(−)−尼古丁、胞二磷胆碱、DMPP和乙酰胆碱(ACh)(加酯酶抑制剂和M受体阻断剂)以浓度依赖的方式(EC506.5μm、8.2μm、9.3μm和27μm)增加NA的释放，具有相似的作用。3尼古丁对纹状体多巴胺的释放量大于海马NA(EC500.16μm，vs.6.5μm)。(+)-Anatoxin-a增加多巴胺的作用强于NA(EC500.05μm比0.39μm)，最大效应与尼古丁相似。异槟榔酮(10-320μm)比去甲肾上腺素更有效地释放多巴胺，但没有达到最大效应。−)−洛贝林(10-320μm)可引起多巴胺的释放，但对尼古丁的作用较大且延迟；高浓度的洛贝林不增加NA的释放，反而抑制其释放。高K+(10 MM)释放出类似程度的多巴胺和去甲肾上腺素。4在突触体内加入5-羟色胺再摄取阻断剂西酞普兰(1μm)，既不影响基础NA的释放，也不影响尼古丁诱发的NA释放。5烟碱拮抗剂甲戊胺(10μm)可完全阻断高浓度尼古丁、乙酰胆碱、胞二磷胆碱、异槟榔酮和类毒素-a引起的NA和多巴胺的释放。虽然甲基苯丙胺(100μm)引起的NA释放完全是甲戊胺敏感的，但DMPP引起的多巴胺释放仅被部分阻断。洛贝林(320μm)引起的多巴胺释放对甲乙胺完全不敏感。6烟碱拮抗剂二氢β-乙二胺和甲基乌头碱对尼古丁诱发的多巴胺释放的抑制作用约为NA释放的30倍。相反，拮抗剂氯异丹明表现出反向敏感性，而曲美他潘和甲氨基甲胺并不优先阻断这两种反应。这些拮抗剂在高浓度时均不能显著改变高K+引起的释放。7高浓度尼古丁(10 0μm)可阻断甲基乌头碱和二氢乌头碱-乙二胺四乙胺对尼古丁诱发的递质释放的阻断作用，而甲乙胺、氯异丹明和曲美沙潘则不能阻断这一作用。尼古丁诱发的NA释放不受河豚毒素的影响，而藜芦碱诱导的NA释放几乎被取消。9我们得出结论，与纹状体多巴胺和海马NA终末相关的突触前烟碱受体在药理上是不同的。原位杂交研究表明，黑质纹状体多巴胺能神经元主要表达α4、α5和β2烟碱型胆碱能受体亚单位，而海马区投射的去甲肾上腺素(NA)神经元主要表达α3、β2和β4亚单位。重组受体的药理学比较表明，含有α3和β4亚基的受体可能调节了海马NA的释放。
1 The aim of the present experiment was to characterize nicotine‐evoked [3H]‐noradrenaline ([3H]‐NA) release from rat superfused hippocampal synaptosomes, using striatal [3H]‐dopamine release for comparison. 2 (−)−Nicotine, cytisine, DMPP and acetylcholine (ACh) (with esterase inhibitor and muscarinic receptor blocker) increased NA release in a concentration‐dependent manner (EC50 6.5 μm, 8.2 μm, 9.3 μm, and 27 μm, respectively) with similar efficacy. 3 Nicotine released striatal dopamine more potently than hippocampal NA (EC50 0.16 μm, vs. 6.5 μm). (+)‐Anatoxin‐a also increased dopamine more potently than NA (EC50 0.05 μm vs 0.39 μm), and maximal effects were similar to those of nicotine. Isoarecolone (10–320 μm) released dopamine more effectively than NA but a maximal effect was not reached. (−)−Lobeline (10–320 μm) evoked dopamine release, but the effect was large and delayed with respect to nicotine; NA release was not increased but rather depressed at high concentrations of lobeline. High K+ (10 mM) released dopamine and NA to similar extents. 4 Addition of the 5‐hydroxytryptamine (5‐HT) reuptake blocker, citalopram (1 μm) to hippocampal synaptosomes affected neither basal NA release nor nicotine‐evoked release. 5 The nicotinic antagonist, mecamylamine (10 μm), virtually abolished NA and dopamine release evoked by high concentrations of nicotine, ACh, cytisine, isoarecolone, and anatoxin‐a. Although NA release evoked by DMPP (100 μm) was entirely mecamylamine‐sensitive, DMPP‐evoked dopamine release was only partially blocked. Dopamine release evoked by lobeline (320 μm) was completely mecamylamine‐insensitive. 6 The nicotinic antagonists dihydro‐β‐erythroidine and methyllycaconitine inhibited nicotine‐evoked dopamine release approximately 30 fold more potently than NA release. In contrast, the antagonist chlorisondamine, displayed a reverse sensitivity, whereas trimetaphan and mecamylamine did not preferentially block either response. None of these antagonists, given at a high concentration, significantly altered release evoked by high K+. 7 Blockade of nicotine‐evoked transmitter release by methyllycaconitine and dihydro‐β‐erythroidine was surmounted by a high concentration of nicotine (100 μm), but blockade by mecamylamine, chlorisondamine, and trimetaphan was insurmountable. 8 Nicotine‐evoked NA release was unaffected by tetrodotoxin, whereas veratridine‐evoked NA release was virtually abolished. 9 We conclude that presynaptic nicotinic receptors associated with striatal dopamine and hippocampal NA terminals differ pharmacologically. In situ hybridization studies suggest that nigrostriatal dopaminergic neurones express mainly α4, α5, and β2 nicotinic cholinoceptor subunits, whereas hippocampal‐projecting noradrenaline (NA) neurones express α3, β2 and β4 subunits. Pharmacological comparisons of recombinant receptors suggest that release of hippocampal NA may be modulated by receptors containing α3 and β4 subunits.
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增强烟碱乙酰胆碱受体介导的[3H]去甲肾上腺素从新生大鼠下丘脑的释放。
DOI：
10.1016/j.neuropharm.2005.08.013
发表时间：
2006
期刊：
Neuropharmacology.
影响因子：
--
作者：
O'Leary,KT;Leslie,FM
通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
M. Alkondon;E. Pereira;S. Wonnacott;Edson X. Albuquerque
影响因子：
3.6
作者：
Christopher M. Flores;Scott W. Rogers;L. Pabreza;B. Wolfe;K. Kellar
通讯作者：
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DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Marks,MJ;Farnham,DA;Grady,SR;Collins,AC
通讯作者：
Collins,AC
用曲美沙芬检测禽类侧螺状核中烟碱受体的功能异质性。
影响因子：
3.6
作者：
Weaver,WR;Wolf,KM;Chiappinelli,VA
通讯作者：
Chiappinelli,VA