ArticleJournal of the American Society of Nephrology : JASN2010
Deletion of the pH sensor GPR4 decreases renal acid excretion.
Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 118 citations in OpenAlex.
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Epac2 Deficiency Compromises Adaptation to Dietary Acidification by Decreasing H+ Transport in the Renal Nephron.Function (Oxford, England) · 2025Article
- Article
- Molecular mechanism of pH sensing and activation in GPR4 reveals proton-mediated GPCR signaling.Cell discovery · 2025Article
- Control of Inflammatory Response by Tissue Microenvironment.bioRxiv : the preprint server for biology · 2025Article
- Roles of sensory receptors in non-sensory organs: the kidney and beyond.Nature reviews. Nephrology · 2025Review
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Intrinsic Molecular Proton Sensitivity Underlies GPR4 Effects on Retrotrapezoid Nucleus Neuronal Activation and COThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Review
- Effects of extracellular metabolic acidosis and out-of-equilibrium COFrontiers in physiology · 2024Article
- The proximal tubule through an NBCe1-dependent mechanism regulates collecting duct phenotypic and remodeling responses to acidosis.American journal of physiology. Renal physiology · 2023Article
- Kidney metabolism and acid-base control: back to the basics.Pflugers Archiv : European journal of physiology · 2022Review
- Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022Review
- Understudied G Protein-Coupled Receptors in the Kidney.Nephron · 2022Review
- Proton-Sensing GPCRs in Health and Disease.Cells · 2021Review
- Endoplasmic reticulum stress signals in the tumour and its microenvironment.Nature reviews. Cancer · 2021Review
- Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Article
- Can GPR4 Be a Potential Therapeutic Target for COVID-19?Frontiers in medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.
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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.