Pharmacological evidence of specific acetylcholine transport in rat cerebral cortex and other brain regions.
Pharmacological evidence of specific acetylcholine transport in rat cerebral cortex and other brain regions.
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大鼠大脑皮层和其他脑区域特异性乙酰胆碱转运的药理学证据。
DOI：
10.1111/jnc.13843
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发表时间：
2016
影响因子：
4.7
通讯作者：
Matomo Nishio.
中科院分区：
文献类型：
--
作者：
Ikunobu Muramatsu;Hatsumi Yoshiki;Junsuke Uwada;Takayoshi Masuoka;Kiyonao Sada;Takanobu Taniguchi;Matomo Nishio.
功能性乙酰胆碱受体（AChRs）不仅存在于细胞膜上，也存在于脑组织细胞内。为了激活细胞内AChRs，内源性亲水性ACh必须穿过质膜。在这里，我们研究了这个过程的药理学特征，包括它是否是由主动乙酰胆碱摄取介导的。当乙酰胆碱酯酶（AChE）被二异丙基氟磷酸盐抑制时，[3 H]乙酰胆碱被有效地吸收到大鼠大脑皮层和其他脑区的片段中，而不是外周组织，如肝脏和肾脏。大鼠大脑皮层对[3 H]ACh的摄取具有温度依赖性，摄取能力与[3 H]胆碱相当。然而，与[~ 3 H]胆碱的摄取相比，低浓度的ACh、卡巴胆碱、四乙基铵（TEA）抑制[~ 3 H]ACh的摄取。胆碱、HC-3、奎尼丁、decycyramidine 22、可乐定、苯海拉明等有机阳离子也能抑制[~ 3 H]ACh的摄取，而皮质酮、精胺、阿托品、河豚毒素等氨基酸和生物胺对[~ 3 H]ACh的摄取影响不大。与氟磷酸二异丙酯不同，几种乙酰胆碱酯酶抑制剂，包括治疗阿尔茨海默病的药物，如多奈哌齐、加兰他敏和卡巴拉汀，也抑制[3 H]乙酰胆碱的摄取，但不抑制[3 H]胆碱的摄取。这些结果表明，在大脑中，乙酰胆碱是专门采取了通过一个独特的运输系统与已知的有机阳离子转运蛋白（OCT）不同的药理学特性，并建议，这种机制可能涉及在脑细胞内胆碱能传输。
Functional acetylcholine receptors (AChRs) were recently demonstrated to exist not only in the plasma membrane but also intracellularly in brain tissues. In order to activate intracellular AChRs, endogenous hydrophilic ACh must cross the plasma membrane. Here, we examined the pharmacological characteristics of this process, including whether it is mediated by active ACh uptake. When ACh esterase (AChE) was suppressed by diisopropylfluorophosphate, [3H]ACh was effectively taken up into segments of rat cerebral cortex and other brain regions, in contrast to peripheral tissues such as liver and kidney. The uptake of [3H]ACh in rat cerebral cortex was temperature‐dependent, and the uptake capacity was comparable to that of [3H]choline. However, [3H]ACh uptake was inhibited by lower concentrations of ACh, carbachol, tetraethylammonium (TEA), compared with uptake of [3H]choline. Uptake of [3H]ACh was also inhibited by several organic cations, including choline, hemicholinium‐3 (HC‐3), quinidine, decynium 22, clonidine, diphenhydramine, but was little affected by some amino acids and biogenic amines, corticosterone, spermine, atropine, and tetrodotoxin. Unlike diisopropylfluorophosphate, several ACh esterase inhibitors, including drugs for Alzheimer's disease, such as donepezil, galantamine, and rivastigmine, also suppressed the uptake of [3H]ACh, but not [3H]choline. These results indicate that in the brain, ACh is specifically taken up through a unique transport system with different pharmacological properties from known organic cation transporters (OCTs), and suggest that this mechanism may be involved in intracellular cholinergic transmission in the brain.