Release of [H-3]-noradrenaline from rat hippocampal synaptosomes by nicotine: Mediation by different nicotinicreceptor subtypes from striatal [H-3]-dopamine release
Release of [H-3]-noradrenaline from rat hippocampal synaptosomes by nicotine: Mediation by different nicotinicreceptor subtypes from striatal [H-3]-dopamine release
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DOI：
10.1111/j.1476-5381.1996.tb15232.x
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发表时间：
1996-02-01
影响因子：
7.3
通讯作者：
Reuben, M
中科院分区：
文献类型：
--
作者：
Clarke, PBS;Reuben, M
本实验的目的是用纹状体[H-3]-多巴胺释放来比较大鼠海马突触体中尼古丁诱发的[H-3]-去甲肾上腺素（[H-3]-NA）释放（-）-烟碱、胱氨酸、DMPP和乙酰胆碱（ACh）（联合酯酶抑制剂和毒蕈碱受体阻滞剂）均呈浓度依赖性增加NA释放（EC（50）分别为6.5 μ M、8.2 μ M、9.3 μ M和27 μ M），且效果相似尼古丁对纹状体多巴胺的释放比海马NA更强（EC(50) 0.16 μ M VS. 6.5 μ M）， (+)-Anatoxin-a对多巴胺的释放也比NA更强（EC(50) 0.05 μ M VS. 0.39 μ M），最大作用与尼古丁相似。异戊酸酮（10-320 μ M）比NA释放多巴胺更有效，但未达到最大效果。（-）-罗贝林（10 ~ 320 μ M）诱发多巴胺释放，但相对于尼古丁，作用大且延迟；高浓度洛莲碱对NA的释放不增加，反而抑制。高K+ (10 mM)释放多巴胺和NA的程度相似海马突触体添加5-羟色胺（5-HT）再摄取阻滞剂西酞普兰（1 μ M）既不影响基础NA释放，也不影响尼古丁诱发的释放烟碱拮抗剂甲胺（10 μ M）几乎可以消除由高浓度尼古丁、乙酰胆碱、胱氨酸、异戊二醇酮和阿那托辛-a引起的NA和多巴胺释放。虽然DMPP （100 μ M）诱导的NA释放完全是甲胺敏感的，但DMPP诱导的多巴胺释放仅部分被阻断。lobeline （320 μ M）诱导的多巴胺释放完全对甲胺不敏感尼古丁拮抗剂二氢- β -红血碱和甲基莱卡乌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。相比之下，拮抗剂氯异旦明显示出反向敏感性，而曲美沙芬和甲胺并没有优先阻断这两种反应。这些拮抗剂在高浓度给药时，均不显著改变高K+引起的释放。高浓度尼古丁（100 μ M）可克服甲基莱卡乌碱和二氢-红血碱对尼古丁诱发的递质释放的阻断作用，但甲胺、氯异旦胺和曲美他芬的阻断作用是不可克服的尼古丁诱发的NA释放不受河豚毒素的影响，而缬草碱诱发的NA释放几乎被消除。我们得出结论，突触前烟碱受体与纹状体多巴胺和海马NA相关。终末在药理学上不同。原位杂交研究表明，黑质纹状体多巴胺能神经元主要表达α 4、α 5和β 2烟碱受体亚基，而海马投射去甲肾上腺素（NA）神经元表达α 3、β 2和β 4亚基。重组受体的药理学比较表明，海马NA的释放可能受到含有α 3和β 4亚基的受体的调节。
1 The aim of the present experiment was to characterize nicotine-evoked [H-3]-noradrenaline ([H-3]-NA) release from rat superfused hippocampal synaptosomes, using striatal [H-3]-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 (EC(50) 6.5 mu M, 8.2 mu M, 9.3 mu M, and 27 mu M, respectively) with similar efficacy.3 Nicotine released striatal dopamine more potently than hippocampal NA (EC(50) 0.16 mu M VS. 6.5 mu M). (+)-Anatoxin-a also increased dopamine more potently than NA (EC(50) 0.05 mu M VS 0.39 mu M), and maximal effects were similar to those of nicotine. Isoarecolone (10-320 mu M) released dopamine more effectively than NA but a maximal effect was not reached. (-)-Lobeline (10-320 mu M) 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 mu M) to hippocampal synaptosomes affected neither basal NA release nor nicotine-evoked release.5 The nicotinic antagonist, mecamylamine (10 mu M), 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 mu M) was entirely mecamylamine-sensitive, DMPP-evoked dopamine release was only partially blocked. Dopamine release evoked by lobeline (320 mu M) was completely mecamylamine-insensitive.6 The nicotinic antagonists dihydro-beta-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-beta-erythroidine was surmounted by a high concentration of nicotine (100 mu M), 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 alpha 4, alpha 5, and beta 2 nicotinic cholinoceptor subunits, whereas hippocampal-projecting noradrenaline (NA) neurones express alpha 3, beta 2 and beta 4 subunits. Pharmacological comparisons of recombinant receptors suggest that release of hippocampal NA may be modulated by receptors containing alpha 3 and beta 4 subunits.