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The Roles of Proton-Sensing G-Protein-Coupled Receptors in Inflammation and Cancer
Calvin R Justus1, Mona A Marie1, Edward J Sanderlin1
1Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Genes
|September 28, 2024
Summary
Proton-sensing G-protein-coupled receptors (GPCRs) like GPR4, GPR65, and GPR68 play key roles in inflammation and cancer by detecting acidic environments. Understanding these receptors may lead to new disease treatments.
Area of Science:
- Physiology
- Molecular Biology
- Oncology
Background:
- Precise pH homeostasis is vital for physiological functions.
- Pathological conditions like inflammation and cancer disrupt tissue pH, leading to acidic microenvironments.
- Proton-sensing G-protein-coupled receptors (GPCRs) act as cellular sensors for these acidic conditions.
Purpose of the Study:
- To review current research on proton-sensing GPCRs (GPR4, GPR65, GPR68) in inflammation and cancer.
- To explore the roles of these receptors in various pathological conditions.
- To discuss the therapeutic potential of targeting these GPCRs.
Main Methods:
- Literature review of current research on proton-sensing GPCRs.
- Analysis of the roles of GPR4, GPR65 (TDAG8), and GPR68 (OGR1) in inflammation and cancer.
- Evaluation of preclinical data for antagonists and agonists targeting these receptors.
Main Results:
- GPR4 and GPR68 are generally pro-inflammatory, while GPR65 exhibits anti-inflammatory effects in inflammatory disorders.
- Proton-sensing GPCRs demonstrate both anti- and pro-tumorigenic effects.
- Antagonists and agonists targeting these receptors have been developed and tested in preclinical models.
Conclusions:
- Proton-sensing GPCRs are critical mediators in acidic tissue microenvironments associated with inflammation and cancer.
- These receptors have complex, context-dependent roles in disease pathophysiology.
- Further investigation is needed to fully elucidate their roles and harness them as therapeutic targets.
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