ReviewCells2021
Proton-Sensing GPCRs in Health and Disease.
Review in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Keratan Sulfate: An Electroconductive Glycosaminoglycan at the Interface of Sensory Perception and Neural Signaling.Journal of neuroscience research · 2026Review
- First Structure-Activity-Relationship Study of Potent G2A Antagonists.Journal of medicinal chemistry · 2026Article
- Acidosis Regulates Microtubule Dynamics via the β1 Integrin/RhoA/CRMP-2 Axis.Journal of the American Chemical Society · 2026Article
- Endothelial GPR68 Is Essential for Arteriogenesis and Represents a Therapeutic Target in a Model of Peripheral Artery Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Solid tumors exploit proton-sensing GPR65 for orchestration of an immunosuppressive tumor microenvironment.Signal transduction and targeted therapy · 2026Article
- Article
- Joint Acidosis and GPR68 Signaling in Osteoarthritis: Implications for Cartilage Gene Regulation.Genes · 2026Review
- Establishing FDA-approved oncology drugs as GPR176 inhibitor through homology modelling, molecular docking, MMGBSA, DFT, and molecular dynamics simulation.Scientific reports · 2026Article
- Acidic microenvironment promotes pancreatic cancer cell survival via Akt phosphorylation-mediated suppression of apoptosis.Frontiers in oncology · 2026Article
- pH sensing and inflammation: linking acidic microenvironments to immune reprogramming.Frontiers in immunology · 2026Review
- GPR4 promotes immune exclusion in colon cancer through LOXL2-mediated extracellular matrix remodeling.Nature communications · 2025Article
- Low pH, High Stakes: A Narrative Review Exploring the Acid-Sensing GPR65 Pathway as a Novel Approach in Renal Cell Carcinoma.Cancers · 2025Review
- The role of pancreatic islet macrophages in type 2 diabetes mellitus: from underlying pathological mechanisms to therapeutic target discovery.Metabolism open · 2025Review
- Novel small molecule inhibitor of GPR68 attenuates endothelial dysfunction and lung injury caused by bacterial lipopolysaccharide.Scientific reports · 2025Article
- Intracellular pH regulates ubiquitin-mediated degradation of the MAP kinase ERK3.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy.Cells · 2025Review
- CaBiomolecules · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The group of proton-sensing G-protein coupled receptors (GPCRs) consists of the four receptors GPR4, TDAG8 (GPR65), OGR1 (GPR68), and G2A (GPR132). These receptors are cellular sensors of acidification, a property that has been attributed to the presence of crucial histidine residues. However, the pH detection varies considerably among the group of proton-sensing GPCRs and ranges from pH of 5.5 to 7.8. While the proton-sensing GPCRs were initially considered to detect acidic cellular environments in the context of inflammation, recent observations have expanded our knowledge about their physiological and pathophysiological functions and many additional individual and unique features have been discovered that suggest a more differentiated role of these receptors in health and disease. It is known that all four receptors contribute to different aspects of tumor biology, cardiovascular physiology, and asthma. However, apart from their overlapping functions, they seem to have individual properties, and recent publications identify potential roles of individual GPCRs in mechanosensation, intestinal inflammation, oncoimmunological interactions, hematopoiesis, as well as inflammatory and neuropathic pain. Here, we put together the knowledge about the biological functions and structural features of the four proton-sensing GPCRs and discuss the biological role of each of the four receptors individually. We explore all currently known pharmacological modulators of the four receptors and highlight potential use. Finally, we point out knowledge gaps in the biological and pharmacological context of proton-sensing GPCRs that should be addressed by future studies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.