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本研究旨在探讨α_2受体激动剂可乐定对苯二氮(艹卓)受体激动剂抗焦虑和反相激动剂致焦虑作用影响的可能的分子机理。在10nmol/L至1μmol/L浓度范围内,可乐定对[~3H]氟硝安定与大鼠皮层相应受体低亲和位点结合无显著影响,但非竞争性拮抗其与高亲和位点的结合。在竞争取代实验中,激动剂安定和CL218 872均表现为双位点结合的亲和力,对低亲和位点无显著影响。反相激动剂DMCM竞争结合曲线亦具有双位点结合特性。可乐定可使这种双位点结合转变成三位点结合,出现一个超高亲和位点。可乐定对拮抗剂Ro15-1788竞争结合特性无显著影响。结果提示,α_2受体激动剂可乐定与受体结合可能导致与之相邻的苯二氮(艹卓)受体发生构象变化,这种构象变化有利于激动剂与受体结合,而不利于反相激动剂的结合。
This study was designed to investigate the possible molecular mechanism of the effects of α 2 -receptor agonist clonidine on the anxiety-induced effects of anti-anxiety and anti-phase agonists on benzodiazepine receptor agonists. Clonidine did not significantly affect the binding of [~ 3H] flunitrazepam to low affinity sites of the corresponding receptors in the rat cortex at a concentration range of 10 nmol / L to 1 μmol / L, but non-competitive antagonism of clonidine with high affinity Point combination. In competitive substitution experiments, both agonist stability and CL218 872 showed binding affinity at both sites with no significant effect on low affinity sites. The reverse phase agonist DMCM competitive binding curve also has a two-site binding characteristic. Clonidine converts this double-site binding into a triple-site binding with an ultra-high affinity site. Clonidine had no significant effect on the competitive binding properties of the antagonist Ro15-1788. The results suggest that binding of α 2 receptor agonist clonidine to the receptor may result in a conformational change of the benzodiazepine receptor adjacent to it and this conformational change favors the binding of the agonist to the receptor, Anti-phase agonist binding.