Dalrymple Matthew B, Pfleger Kevin D G, Eidne Karin A
Laboratory for Molecular Endocrinology - GPCRs, Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Pharmacol Ther. 2008 Jun;118(3):359-71. doi: 10.1016/j.pharmthera.2008.03.004. Epub 2008 Apr 8.
With an ever-expanding need for reliable therapeutic agents that are highly effective and exhibit minimal deleterious side effects, a greater understanding of the mechanisms underlying G protein-coupled receptor (GPCR) regulation is fundamental. GPCRs comprise more than 30% of all therapeutic drug targets and it is likely that this will only increase as more orphan GPCRs are identified. The past decade has seen a dramatic shift in the prevailing concept of how GPCRs function, in particular the growing acceptance that GPCRs are capable of interacting with one another at a molecular level to form complexes, with significantly different pharmacological properties to their monomeric selves. While the ability of like-receptors to associate and form homodimers raises some interesting mechanistic issues, the possibility that unlike-receptors could heterodimerise in certain tissue types, producing a functionally unique signalling complex that binds specific ligands, provides an invaluable opportunity to refine and redefine pharmacological interventions with greater specificity and efficacy.
随着对高效且副作用极小的可靠治疗药物的需求不断扩大，深入了解G蛋白偶联受体（GPCR）调节的潜在机制至关重要。GPCR占所有治疗药物靶点的30%以上，而且随着更多孤儿GPCR的发现，这一比例可能还会增加。在过去十年中，GPCR功能的主流概念发生了巨大转变，尤其是越来越多的人接受GPCR能够在分子水平上相互作用形成复合物，其药理学特性与其单体自身有显著不同。虽然同类受体相互结合形成同源二聚体的能力引发了一些有趣的机制问题，但不同受体在某些组织类型中可能形成异源二聚体，产生结合特定配体的功能独特的信号复合物，这为以更高的特异性和疗效优化和重新定义药物干预提供了宝贵机会。
