5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens
5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens
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DOI：
10.1016/s0091-3057(01)00720-1
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发表时间：
2002-05-01
影响因子：
3.6
通讯作者：
Winter, JC
中科院分区：
文献类型：
--
作者：
Rabin, RA;Regina, M;Winter, JC
在稳定表达大鼠5-HT 2A受体的PC 12细胞（PC 12 -5-HT 2A细胞）中研究了5-HT 2A介导的磷酸肌醇水解刺激在致幻剂辨别效应中的作用。致幻化合物D-麦角酸二乙基酰胺（LSD）、（-）2，5-二甲氧基-4-甲基苯丙胺（DOM）、裸盖菇素、N，N-二甲基色胺（DMT）、5-甲氧基-N，N-二甲基色胺（MDMT）和N，N-二乙基色胺（DET）均引起[H-3]肌醇磷酸产生的浓度依赖性增加。非致幻化合物，6-氟-N，N-二乙基色胺（6-F-DET），麦角乙脲和喹嗪，也显示出显着的功效，刺激磷酸肌醇水解，而2-溴-麦角酸二乙基酰胺（BOL），这不是一种致幻剂，没有改变肌醇磷酸的产生。β-咔啉类化合物（harmonic和harmane）也不会改变磷酸肌醇水解。这些结果与以前的药物歧视研究的比较表明，LSD和DOM训练的动物和刺激磷酸肌醇水解的疗效之间的取代度明显缺乏相关性。目前的研究表明，5-HT 2A介导的刺激磷酸肌醇水解似乎并不是唯一的关键信号机制参与的歧视效应的致幻剂。(C)2002年爱思唯尔科学公司All rights reserved.
The role of 5-HT2A-mediated stimulation of phosphoinositide hydrolysis in the discriminative effects of hallucinogens was investigated in PC12 cells stably expressing the rat 5-HT2A receptor (PC12-5-HT2A cells). The hallucinogenic compounds, D-lysergic acid diethylamide (LSD), (-)2,5-dimethoxy-4-methylamphetamine (DOM), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (MDMT) and N,N-diethyltryptamine (DET), all caused a concentration-dependent increase in the generation of [H-3]inisotol phosphates. The nonhallucinogenic compounds, 6-fluoro-N,N-diethyltryptamine (6-F-DET), lisuride and quipazine, also displayed significant efficacy in stimulating phosphoinositide hydrolysis, while 2-bromo-lysergic acid diethylamide (BOL), which is not a hallucinogen, did not alter inositol phosphate generation. The beta-carbolines, harmaline and harmane, also did not alter phosphoinositide hydrolysis. Comparison of these results with previous drug discrimination studies indicated the apparent lack of correlation between the degree of substitution on LSD- and DOM-trained animals and efficacy in stimulating phosphoinositide hydrolysis. The present study indicates that 5-HT2A-mediated stimulation of phosphoinositide hydrolysis does not appear to be the sole critical signaling mechanism involved in the discrimination effects of hallucinogens. (C) 2002 Elsevier Science Inc. All rights reserved.