ArticleProceedings of the National Academy of Sciences of the United States of America2015
Reciprocal regulation of two G protein-coupled receptors sensing extracellular concentrations of Ca2+ and H.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- Acidic extracellular pH-induced PTH secretion in male mouse parathyroids is OGR1-dependent.Endocrinology · 2026Article
- Loss of G-protein coupled receptor 68 in hematopoietic tissues enhances long-term hematopoietic stem cell function upon aging.Stem cell research & therapy · 2025Article
- Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BKPflugers Archiv : European journal of physiology · 2024Article
- Stimulation of the calcium-sensing receptor induces relaxations through CGRP and NK1 receptor-mediated pathways in male rat mesenteric arteries.Physiological reports · 2024Article
- Stimulation of the calcium-sensing receptor induces relaxations of rat mesenteric arteries by endothelium-dependent and -independent pathways via BKPhysiological reports · 2024Article
- BUB1, BUB1B, CCNA2, and CDCA8, along with miR-524-5p, as clinically relevant biomarkers for the diagnosis and treatment of endometrial carcinoma.BMC cancer · 2023Article
- Targeting purine metabolism in ovarian cancer.Journal of ovarian research · 2022Review
- pH and proton-sensitive receptors in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Physiological relevance of proton-activated GPCRs.Pflugers Archiv : European journal of physiology · 2022Review
- The role of CaCell proliferation · 2021Review
- RNA-Seq analysis of knocking out the neuroprotective proton-sensitive GPR68 on basal and acute ischemia-induced transcriptome changes and signaling in mouse brain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The Roles of Orphan G Protein-Coupled Receptors in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2021Review
- GPR68 Contributes to Persistent Acidosis-Induced Activation of AGC Kinases and Tyrosine Phosphorylation in Organotypic Hippocampal Slices.Frontiers in neuroscience · 2021Article
- Article
- Extracellular acidification induces ROS- and mPTP-mediated death in HEK293 cells.Redox biology · 2018Article
- Functional expression of calcium-permeable canonical transient receptor potential 4-containing channels promotes migration of medulloblastoma cells.The Journal of physiology · 2017Article
- Potential Coagulation Factor-Driven Pro-Inflammatory Responses in Ovarian Cancer Tissues Associated with Insufficient O₂ and Plasma Supply.International journal of molecular sciences · 2017Review
- OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages.PloS one · 2016Article
- The Calcium-Sensing Receptor and Integrins in Cellular Differentiation and Migration.Frontiers in physiology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
G protein-coupled receptors (GPCRs) are cell surface receptors that detect a wide range of extracellular messengers and convey this information to the inside of cells. Extracellular calcium-sensing receptor (CaSR) and ovarian cancer gene receptor 1 (OGR1) are two GPCRs that sense extracellular Ca(2+) and H(+), respectively. These two ions are key components of the interstitial fluid, and their concentrations change in an activity-dependent manner. Importantly, the interstitial fluid forms part of the microenvironment that influences cell function in health and disease; however, the exact mechanisms through which changes in the microenvironment influence cell function remain largely unknown. We show that CaSR and OGR1 reciprocally inhibit signaling through each other in central neurons, and that this is lost in their transformed counterparts. Furthermore, strong intracellular acidification impairs CaSR function, but potentiates OGR1 function. Thus, CaSR and OGR1 activities can be regulated in a seesaw manner, whereby conditions promoting signaling through one receptor simultaneously inhibit signaling through the other receptor, potentiating the difference in their relative signaling activity. Our results provide insight into how small but consistent changes in the ionic microenvironment of cells can significantly alter the balance between two signaling pathways, which may contribute to disease progression.
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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.