Nakata Hiruyasu, Yoshioka Kazuaki, Kamiya Toshio
Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, 183-8526, Japan.
Neurotox Res. 2004;6(4):291-7. doi: 10.1007/BF03033439.
It is becoming clear that the functions of G protein-coupled receptors (GPCRs), the largest family of plasma membrane-localized receptors, are regulated by direct oligomeric formation between GPCRs, as either homo- or hetero-oligomers. This review article explores the mechanistic implications of GPCR dimerization, especially among purinergic receptors, adenosine receptors and P2 receptors, which play critical roles in the regulation of neurotransmission in the central nervous system. Briefly, adenosine receptors are able to form a heteromeric complex with P2 receptors that generates an adenosine receptor with P2 receptor-like agonistic pharmacology. This mechanism may be used to fine-tune purinergic inhibition locally at sites where there is a particular oligomerization structure between purinergic receptors, and to explain the undefined adenosine-like purinergic functions of adenine nucleotides. Purinergic receptors also form oligomers with GPCRs of other families present in the brain, such as dopamine receptors and metabotropic glutamate receptors, to alter the functional properties. The effect of GPCR oligomerization on receptor functions is thus considered as an important system in the central nervous system.
越来越明显的是，G蛋白偶联受体（GPCRs）作为质膜定位受体的最大家族，其功能是通过GPCRs之间直接形成同型或异型寡聚体来调节的。这篇综述文章探讨了GPCR二聚化的机制意义，特别是在嘌呤能受体、腺苷受体和P2受体之间，它们在中枢神经系统神经传递的调节中起着关键作用。简而言之，腺苷受体能够与P2受体形成异聚体复合物，产生具有P2受体样激动药理学特性的腺苷受体。这种机制可能用于在嘌呤能受体之间存在特定寡聚化结构的部位局部微调嘌呤能抑制作用，并解释腺嘌呤核苷酸未明确的腺苷样嘌呤能功能。嘌呤能受体还与大脑中存在的其他家族的GPCRs形成寡聚体，如多巴胺受体和代谢型谷氨酸受体，以改变功能特性。因此，GPCR寡聚化对受体功能的影响被认为是中枢神经系统中的一个重要系统。
