期刊
EUROPEAN NEUROPSYCHOPHARMACOLOGY
卷 18, 期 9, 页码 682-691出版社
ELSEVIER
DOI: 10.1016/j.euroneuro.2008.05.001
关键词
clozapine; dopamine receptors; receptor oligomerization; schizophrenia; fluorescence rezonans energy transfer (FRET); HEK 293
Clozapine is effective although stilt not perfect drug used to treat schizophrenia. The precise mechanism of its action is not known. Here we show that there are two binding sites for clozapine at the dopamine D-1 and D-2 receptors, and the affinity of D1R strongly depended on whether the receptor was present alone or together with D2R (or its genetic variant D-2(Ser311Cys)) in the cell membrane, pointing to the rote of receptor hetero-dimerization in the observed phenomenon. The use of fluorescence resonance energy transfer (FRET) technology, observed via fluorescence lifetime microscopy of the single cell, indicated that low concentration of clozapine (10(-9) M), sufficient to saturate the high affinity site, uncoupled the D1R-D2R hetero-dimers. Therefore it has been concluded that clozapine might antagonize the effect of concomitant stimulation of both dopamine receptors, which has been shown previously to enhance the formation of hetero-dimers and to stimulate the calcium signaling pathway. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据