咪唑啉受体及其对阿片药理作用的调节机制  

IMIDAZOLINE RECEPTOR AND THE MECHANISMS OF ITS MODULATION ON OPIOID PHARMACOLOGICAL ACTIONS

作　　者：苏瑞斌[1] 吴宁[1] 李斐[1] 李锦[1] 丛斌[2] 

机构地区：[1]军事医学科学院毒物药物研究所新药评价研究室,北京100850 [2]河北医科大学法医系,石家庄050017

出　　处：《中国药物依赖性杂志》2006年第3期177-181,共5页Chinese Journal of Drug Dependence

基　　金：国家重点基础研究发展计划(973计划)"精神活性物质依赖的生物学基础及防治"(2003CB515400)资助项目

摘　　要：用稳定转染咪唑啉1型受体(I1R)的细胞(CHO-I1),对I1R信号转导途径进行了初步研究。首次直接证实I1R的信号转导途径与活化PC-PLC继而产生DAG,其后引起丝裂原激活蛋白激酶(MAPK)酶促级联反应过程有关。采用共同稳定表达μ阿片受体(MOR)和I1R的CHO细胞表达系统(CHO-μ/I1细胞),对I1R在受体后水平抑制吗啡依赖的可能分子机制进行了研究。首次提供了胍丁胺通过作用于I1R而抑制吗啡依赖的直接实验证据,其分子机制可能主要是胍丁胺激活I1R抑制吗啡慢性处理时cAMP通路和Ca2+信号通路代偿性适应而抑制吗啡依赖的形成。The signal transduction system was evaluated with the cell lines that stably expressed imidazoline 1 receptor （IIR）. We proved for the first time that the signal transduction system of It R was related to activation of PC - PLC, followed by accumulation of DAG and the activation of MAPK cascade process. The possible molecular mechanisms for the intervention of IIR on morphine dependence was evaluated with the cell lines that stably co- expressed IIR and μ opioid receptors （MOR）. For the first time we provided the direct experimental evidence to prove that agmatine inhibited morphine dependence through activation of imidazoline receptor, and the possible mechanisms were related to inhibition on the adaptation of cAMP pathway and calcium signal pathway.

关 键 词：咪唑啉1型受体 G蛋白偶联受体 吗啡依赖 cAMP通路 Ca2+信号通路 

分 类 号：R972.4[医药卫生—药品] R971.1[医药卫生—药学]