Division of Physical Biochemistry, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Trends Pharmacol Sci. 2010 Nov;31(11):499-508. doi: 10.1016/j.tips.2010.08.003. Epub 2010 Oct 1.
There is a large body of experimental evidence that is compatible with the presence of heterodimers of the major A subclass of G protein-coupled receptors (GPCRs) and suggests that these heterodimers might have different functional properties from those of the monomers (or homodimers) of the individual receptors that engage in heterodimer formation. The question is whether there are allosteric interactions across the receptor-receptor interface of a heterodimer that modulate the binding properties of the heterodimer components and thereby change their pharmacology. In this review, I examine published experimental evidence from radioligand binding studies in the context of different models of allosterism and discuss a number of apparently discrepant results. The analysis suggests that more experimental data are required if equal, two-way, crossreceptor interactions within a GPCR heterodimer, at the level of binding, are to be unequivocally demonstrated.
有大量的实验证据表明，主要 A 亚类 G 蛋白偶联受体 (GPCR) 的异二聚体的存在是兼容的，并表明这些异二聚体可能具有与参与异二聚体形成的各个受体的单体 (或同二聚体) 不同的功能特性。问题是，异二聚体的受体-受体界面是否存在变构相互作用，从而调节异二聚体成分的结合特性，并改变它们的药理学。在这篇综述中，我根据不同的变构模型，检查了放射性配体结合研究中的已发表的实验证据，并讨论了一些明显不一致的结果。分析表明，如果要在 GPCR 异二聚体的结合水平上明确证明 GPCR 异二聚体中存在平等的、双向的、交叉受体相互作用，那么需要更多的实验数据。
