G protein-coupled receptor 84 (GPR84) (GPR84)

G protein-coupled receptor 84 (GPR84) is a metabolic sensing protein primarily expressed on the surface of myeloid cells, including neutrophils, monocytes, and macrophages, where it acts as a specific receptor for medium-chain fatty acids (MCFAs) such as octanoic acid [7, 10]. Historically identified as an orphan receptor, it is now recognized for its critical role in linking nutritional lipid signals to the innate immune system, where its activation promotes pro-inflammatory cytokine production and leukocyte chemotaxis [7, 13, 15]. Through its coupling with Gi/o proteins, GPR84 modulates pathways involved in chronic inflammatory and fibrotic conditions, including idiopathic pulmonary fibrosis, non-alcoholic steatohepatitis (NASH), and inflammatory bowel disease [10, 15]. Octanoic acid, a natural eight-carbon saturated fatty acid also known as caprylic acid, serves as a direct agonist for GPR84 and has been independently investigated as a therapeutic agent for essential tremor [1, 17]. While octanoic acid's tremor-suppressing efficacy may involve neurological mechanisms distinct from GPR84 signaling, such as the modulation of T-type calcium channels, the receptor remains a primary target for pharmaceutical efforts focused on developing small-molecule antagonists to inhibit pathogenic inflammation and tissue scarring [3, 10, 20].

Other names

GPR84EX33Medium-chain fatty acid receptorOctanoic acid receptorCaprylic acid receptorG protein-coupled receptor 84

GPR84 functions as a Gi/o-coupled receptor that is activated by medium-chain fatty acids (C8-C12). Agonists like octanoic acid induce the inhibition of adenylate cyclase, leading to reduced intracellular cAMP levels and the subsequent activation of pro-inflammatory signaling cascades and myeloid cell chemotaxis [7, 10]. Antagonists (e.g., PBI-4050) competitively or allosterically inhibit these pathways to reduce the recruitment of inflammatory cells and the secretion of fibrotic markers [10, 15].