Dale Natasha C, Hoyer Daniel, Jacobson Laura H, Pfleger Kevin D G, Johnstone Elizabeth K M
Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, Australia.
Australian Research Council Centre for Personalised Therapeutics Technologies, Melbourne, VIC, Australia.
Front Cell Neurosci. 2022 Apr 13;16:812359. doi: 10.3389/fncel.2022.812359. eCollection 2022.
The orexin system comprises two G protein-coupled receptors, OX and OX receptors (OXR and OXR, respectively), along with two endogenous agonists cleaved from a common precursor (prepro-orexin), orexin-A (OX-A) and orexin-B (OX-B). For the receptors, a complex array of signaling behaviors has been reported. In particular, it becomes obvious that orexin receptor coupling is very diverse and can be tissue-, cell- and context-dependent. Here, the early signal transduction interactions of the orexin receptors will be discussed in depth, with particular emphasis on the direct G protein interactions of each receptor. In doing so, it is evident that ligands, additional receptor-protein interactions and cellular environment all play important roles in the G protein coupling profiles of the orexin receptors. This has potential implications for our understanding of the orexin system's function in both central and peripheral environments, as well as the development of novel agonists, antagonists and possibly allosteric modulators targeting the orexin system.
食欲素系统由两种G蛋白偶联受体，即OX1和OX2受体（分别为OX1R和OX2R），以及从共同前体（前食欲素原）切割而来的两种内源性激动剂，食欲素-A（OX-A）和食欲素-B（OX-B）组成。关于这些受体，已有一系列复杂的信号传导行为被报道。特别明显的是，食欲素受体的偶联非常多样，且可能依赖于组织、细胞和环境。在此，将深入讨论食欲素受体的早期信号转导相互作用，尤其着重于每个受体的直接G蛋白相互作用。这样做时，很明显配体、额外的受体-蛋白质相互作用和细胞环境在食欲素受体的G蛋白偶联模式中都起着重要作用。这对于我们理解食欲素系统在中枢和外周环境中的功能，以及开发针对食欲素系统的新型激动剂、拮抗剂和可能的变构调节剂具有潜在意义。
