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受体镶嵌体的整合作用:受体拓扑结构和变构调节剂的相关性

Integrative action of receptor mosaics: relevance of receptor topology and allosteric modulators.

作者信息

Francesco Agnati Luigi, Diego Guidolin, Susanna Genedani, Giuseppina Leo, Amina Woods S, Sergi Ferrè, Rafael Franco, Kjell Fuxe

机构信息

Department of Biomedical Sciences, University of Modena and Reggio Emilia and IRCCS Lido, Venezia, Italy.

出版信息

J Recept Signal Transduct Res. 2008;28(6):543-65. doi: 10.1080/10799890802590420.

Abstract

After a definition of the receptor mosaic (RM, high order heteromer or homomer) concept, this study analyzes some relevant theoretical aspects related to receptor-receptor interactions (RRIs). In particular, the possible influence of the plasma membrane microdomain on RM integrative functions are discussed. Furthermore, a possible mathematical approach may identify the RM topologies [i.e., the spatial arrangements the receptors (tesserae of the mosaic) can assume within the RM assembly]. Finally, data are presented on homocysteine possible biasing action on the well-characterized heterodimer/receptor mosaic formed by adenosine A2A and dopamine D2 receptors. We discuss how these findings can lead to a new possible approach for developing drugs for the treatment of certain neuropsychiatric disorders.

摘要

在对受体镶嵌体(RM,高阶异源二聚体或同源二聚体)概念进行定义之后,本研究分析了与受体 - 受体相互作用(RRIs)相关的一些重要理论方面。特别地,讨论了质膜微区对RM整合功能的可能影响。此外,一种可能的数学方法可以确定RM拓扑结构[即受体(镶嵌体的镶嵌单元)在RM组装中可能呈现的空间排列]。最后,给出了关于同型半胱氨酸对由腺苷A2A和多巴胺D2受体形成的特征明确的异源二聚体/受体镶嵌体可能的偏向作用的数据。我们讨论了这些发现如何能够为开发治疗某些神经精神疾病的药物带来一种新的可能方法。

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