Eicosanoids are a family of bioactive compounds derived from arachidonic acid (AA) that play pivotal roles in physiology and disease, including inflammatory conditions of multiple organ systems. The biosynthesis of eicosanoids requires a series of catalytic steps that are controlled by designated enzymes, which can be regulated by inflammatory and stress signals via transcriptional and translational mechanisms. In the past decades, evidence have emerged indicating that G-protein coupled receptors (GPCRs) can sense extracellular metabolites, and regulate inflammatory responses including eicosanoid production. This review focuses on the recent advances of metabolite GPCRs research, their role in regulation of eicosanoid biosynthesis, and the link to pathophysiological conditions.
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http://dx.doi.org/10.1016/j.bcp.2022.115208 | DOI Listing |
J Biochem Mol Toxicol
January 2025
Department of Cardiothoracic Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou City, Hubei Province, China.
Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease (CVD) that is partly attributable to endothelial dysfunction, inflammatory response, and angiogenesis. G protein-coupled receptor 4 (GPR4), a proton-sensitive G protein-coupled receptor that is abundantly expressed in vascular endothelial cells, has been associated with numerous physiological functions. Nevertheless, its potential involvement in the development of AAA remains unexplored.
View Article and Find Full Text PDFNat Commun
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
J Biol Chem
January 2025
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Electronic address:
Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
Neuropathic pain, a challenging condition often associated with diabetes, trauma, or chemotherapy, impairs patients' quality of life. Current treatments often provide inconsistent relief and notable adverse effects, highlighting the urgent need for safer and more effective alternatives. This review investigates marine-derived bioactive compounds as potential novel therapies for neuropathic pain management.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Autoimmune diseases are complex conditions characterized by immune-mediated tissue damage and chronic inflammation. Protease-activated receptor 2 (Par2) has been implicated in these diseases, exhibiting dual roles that complicate its therapeutic potential. This review examines the perplexing functions of Par2, which promotes inflammation through immune cell activation while facilitating tissue healing in damaged organs.
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