Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Br J Pharmacol. 2024 May;181(10):1524-1535. doi: 10.1111/bph.16206. Epub 2023 Aug 28.
Members of the GPCR superfamily have a wide variety of physiological roles and are therefore valuable targets for developing effective medicines. However, within this superfamily are receptors that are less well characterized and remain orphans, including GPR84. This receptor is stimulated by ligands derived from dietary nutrients, specifically medium chain fatty acids (C9-14), and novel synthetic agonists. There are data demonstrating the role of GPR84 in inflammatory pathways, in addition to emerging data suggesting a key role for GPR84 as a nutrient-sensing GPCR involved in metabolism by sensing energy load via nutrient exposure and subsequent signalling leading to modulation of food intake. Exploring GPR84 pharmacology, its localization and what drives its expression has revealed multiple roles for this receptor. Here, we will reflect on these various roles of GRP84 demonstrated thus far, primarily by exploring data from pre-clinical and clinical studies in various physiological systems, with a specific focus on the gastrointestinal tract. LINKED ARTICLES: This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc.
G 蛋白偶联受体超家族的成员具有广泛的生理作用,因此是开发有效药物的有价值的靶点。然而,在这个超家族中,有一些受体的特征不太明显,仍然是孤儿受体,包括 GPR84。这种受体被来自膳食营养素的配体刺激,特别是中链脂肪酸(C9-14)和新型合成激动剂。有数据表明 GPR84 在炎症途径中的作用,此外还有新出现的数据表明 GPR84 作为一种参与代谢的营养感应 GPCR 的关键作用,通过感应营养暴露和随后的信号传导来感知能量负荷,从而调节食物摄入。探索 GPR84 的药理学、定位和驱动其表达的因素揭示了该受体的多种作用。在这里,我们将反思迄今为止 GPR84 的这些各种作用,主要是通过探索各种生理系统中临床前和临床研究的数据,特别关注胃肠道。相关文章:本文是 GPR84 药理学专题的一部分。要查看本节中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc.