Gpr18, a G-protein-coupled receptor, belongs to the orphan class A family of the GPCR superfamily. It has been suggested to be related to the endocannabinoid system, despite low sequence homology with cannabinoid receptors CB1R and CB2R [2]. Gpr18 may play a role in the migration and proliferation of cancer cells, macrophages, and other inflammation-associated immune cells, making it a potential target for inflammation, cancer, and analgesia therapy [1].

In various health disorders, studies have shown significant findings related to Gpr18. In cardiovascular and metabolic diseases, the resolvin D2-GPR18 axis has a protective role, and Gpr18 agonists like PSB-KD-107 can dilate blood vessels and may affect blood pressure and heart function, with the vasorelaxant effect mainly related to endothelial nitric oxide generation [3,4]. In Duchenne muscular dystrophy, the Gpr18 agonist PSB-KD107 can dampen inflammation, enhance myogenesis, and restore muscle function [6]. Also, verbenalin, through binding to Gpr18, alleviates acute lung injury induced by sepsis and IgG immune complex [5].

In conclusion, Gpr18 is a key receptor with potential therapeutic implications in multiple disease areas such as inflammation-related diseases, cardiovascular and metabolic diseases, and muscular dystrophy. Research on Gpr18, especially through the use of agonists in in vivo studies, has revealed its role in modulating inflammation, muscle function, and vascular tone, providing new insights into disease mechanisms and potential treatment strategies.

References:

1. Zhang, Linjie, Fang, Yiwen, Hang, Sijing, Sheng, Ruilong, Guo, Ruihua. . GPR18 and GPR55-related Ligands Serving as Antagonists or Agonists: Current Situation, Challenges and Perspectives. In Medicinal chemistry (Shariqah (United Arab Emirates)), 19, 838-847. doi:10.2174/1573406419666230406095220. https://pubmed.ncbi.nlm.nih.gov/37038675/

2. Morales, Paula, Lago-Fernandez, Ana, Hurst, Dow P, Abood, Mary E, Jagerovic, Nadine. 2020. Therapeutic Exploitation of GPR18: Beyond the Cannabinoids? In Journal of medicinal chemistry, 63, 14216-14227. doi:10.1021/acs.jmedchem.0c00926. https://pubmed.ncbi.nlm.nih.gov/32914978/

3. Zhao, Mengmeng, Zheng, Zihui, Yin, Zheng, Wan, Jun, Wang, Menglong. 2023. Resolvin D2 and its receptor GPR18 in cardiovascular and metabolic diseases: A promising biomarker and therapeutic target. In Pharmacological research, 195, 106832. doi:10.1016/j.phrs.2023.106832. https://pubmed.ncbi.nlm.nih.gov/37364787/

4. Kotańska, Magdalena, Kubacka, Monika, Bednarski, Marek, Müller, Christa E, Kieć-Kononowicz, Katarzyna. 2021. The GPR18 Agonist PSB-KD-107 Exerts Endothelium-Dependent Vasorelaxant Effects. In Pharmaceuticals (Basel, Switzerland), 14, . doi:10.3390/ph14080799. https://pubmed.ncbi.nlm.nih.gov/34451896/

5. Yang, Lei, Liu, Tianyu, Zhuo, Yuzhen, Lin, Jianping, Wang, Ximo. 2023. Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor. In Cellular signalling, 109, 110768. doi:10.1016/j.cellsig.2023.110768. https://pubmed.ncbi.nlm.nih.gov/37315751/

6. Dort, Junio, Orfi, Zakaria, Fiscaletti, Melissa, Campeau, Philippe M, Dumont, Nicolas A. 2023. Gpr18 agonist dampens inflammation, enhances myogenesis, and restores muscle function in models of Duchenne muscular dystrophy. In Frontiers in cell and developmental biology, 11, 1187253. doi:10.3389/fcell.2023.1187253. https://pubmed.ncbi.nlm.nih.gov/37645248/