咪唑啉受体及其对阿片药理作用的调节机制

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。

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

The signal transduction system was evaluated with the cell lines that stably expressed imidazoline 1 receptor(I_1R).We proved for the first time that the signal transduction system of I_1R 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 I_1R on morphine dependence was evaluated with the cell lines that stably co-expressed I_1R 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.