Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function

During periods of exercise, the primary cause of metabolic acidosis is the accumulation of lactate from anaerobic metabolism, whereas a transient increase in CO<sub>2</sub> triggers a mild respiratory acidosis through the production of carbonic acid (H<sub>2</sub>CO<sub>...

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Main Authors: Fengzhi Yu, Dandan Jia, Ru Wang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/6/813
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author Fengzhi Yu
Dandan Jia
Ru Wang
author_facet Fengzhi Yu
Dandan Jia
Ru Wang
author_sort Fengzhi Yu
collection DOAJ
description During periods of exercise, the primary cause of metabolic acidosis is the accumulation of lactate from anaerobic metabolism, whereas a transient increase in CO<sub>2</sub> triggers a mild respiratory acidosis through the production of carbonic acid (H<sub>2</sub>CO<sub>3</sub>). The combined effects of these reactions result in a slight acidifying shift in arterial blood pH. Proton-sensing G protein-coupled receptors (including GPR68, GPR4, GPR132, and GPR65) represent the primary receptors within the body for detecting alterations in extracellular proton concentrations. These receptors have been demonstrated to possess potential roles in mechanosensation, intestinal inflammation, oncoimmunological interactions, hematopoiesis, as well as inflammatory and neuropathic pain. Recent studies have shown that the activation or inhibition of these receptors modulates a number of arterial functions, including angiogenesis, arterial relaxation, and arterial inflammation. It is well established that moderate exercise has a beneficial effect on the regulation of arterial function. This study examines the effect of exercise on proton concentrations in the microenvironment of the organism and its influence on proton-sensing G protein-coupled receptors located on cell membranes, as well as possible mechanisms involved in the regulation of arterial function. The objective is to present novel perspectives for the exploration of potential drug targets for the prevention and treatment of arterial dysfunction and the development of exercise regimens.
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spelling doaj-art-783c4b31f2cc456895ed405468bf5ea22025-08-20T02:24:42ZengMDPI AGBiomolecules2218-273X2025-06-0115681310.3390/biom15060813Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial FunctionFengzhi Yu0Dandan Jia1Ru Wang2School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaSchool of Exercise and Health, Shanghai University of Sport, Shanghai 200438, ChinaDuring periods of exercise, the primary cause of metabolic acidosis is the accumulation of lactate from anaerobic metabolism, whereas a transient increase in CO<sub>2</sub> triggers a mild respiratory acidosis through the production of carbonic acid (H<sub>2</sub>CO<sub>3</sub>). The combined effects of these reactions result in a slight acidifying shift in arterial blood pH. Proton-sensing G protein-coupled receptors (including GPR68, GPR4, GPR132, and GPR65) represent the primary receptors within the body for detecting alterations in extracellular proton concentrations. These receptors have been demonstrated to possess potential roles in mechanosensation, intestinal inflammation, oncoimmunological interactions, hematopoiesis, as well as inflammatory and neuropathic pain. Recent studies have shown that the activation or inhibition of these receptors modulates a number of arterial functions, including angiogenesis, arterial relaxation, and arterial inflammation. It is well established that moderate exercise has a beneficial effect on the regulation of arterial function. This study examines the effect of exercise on proton concentrations in the microenvironment of the organism and its influence on proton-sensing G protein-coupled receptors located on cell membranes, as well as possible mechanisms involved in the regulation of arterial function. The objective is to present novel perspectives for the exploration of potential drug targets for the prevention and treatment of arterial dysfunction and the development of exercise regimens.https://www.mdpi.com/2218-273X/15/6/813exerciseproton-sensing G protein-coupled receptorsvascular endothelial cellvascular smooth muscle cellarterial function
spellingShingle Fengzhi Yu
Dandan Jia
Ru Wang
Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function
Biomolecules
exercise
proton-sensing G protein-coupled receptors
vascular endothelial cell
vascular smooth muscle cell
arterial function
title Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function
title_full Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function
title_fullStr Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function
title_full_unstemmed Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function
title_short Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function
title_sort proton sensing g protein coupled receptors and their potential role in exercise regulation of arterial function
topic exercise
proton-sensing G protein-coupled receptors
vascular endothelial cell
vascular smooth muscle cell
arterial function
url https://www.mdpi.com/2218-273X/15/6/813
work_keys_str_mv AT fengzhiyu protonsensinggproteincoupledreceptorsandtheirpotentialroleinexerciseregulationofarterialfunction
AT dandanjia protonsensinggproteincoupledreceptorsandtheirpotentialroleinexerciseregulationofarterialfunction
AT ruwang protonsensinggproteincoupledreceptorsandtheirpotentialroleinexerciseregulationofarterialfunction