Svensson A L, Zhang X, Nordberg A
Department of Clinical Neuroscience and Family Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden.
Brain Res. 1996 Jul 8;726(1-2):207-12.
Rat cortical synaptosomes preloaded with [3H]choline were superfused and stimulated with K+ in order to investigate the effect of the cholinesterase inhibitor tacrine on the in vitro release of acetylcholine (ACh). Tacrine was found to biphasically both increase (10(-6) and 5 x 10(-6) M) and decrease (10(-5)-10(-4) M) the release of ACh in a concentration-dependent manner. The facilitatory effect of tacrine was prevented by atropine and the M1 antagonist pirenzepine, whereas the inhibitory effect induced by tacrine was blocked by atropine and the M2 antagonist AF-DX 116. These results indicate that tacrine causes a biphasic effect on K+ stimulated ACh release in the brain via M1 and M2 muscarinic receptors. The tacrine induced enhancement of the ACh release occurs at clinical relevant tacrine concentrations and might therefore be of importance for the treatment outcome of Alzheimer's disease.
预先加载了[3H]胆碱的大鼠皮质突触体被进行了灌流，并使用钾离子进行刺激，以研究胆碱酯酶抑制剂他克林对乙酰胆碱（ACh）体外释放的影响。发现他克林以浓度依赖的方式对ACh的释放产生双相作用，既增加（10^(-6)和5×10^(-6) M）又减少（10^(-5)-10^(-4) M）。他克林的促进作用被阿托品和M1拮抗剂哌仑西平所阻断，而他克林诱导的抑制作用被阿托品和M2拮抗剂AF-DX 116所阻断。这些结果表明，他克林通过M1和M2毒蕈碱受体对大脑中钾离子刺激的ACh释放产生双相作用。他克林诱导的ACh释放增强发生在与临床相关的他克林浓度下，因此可能对阿尔茨海默病的治疗结果具有重要意义。
