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BACKGROUND & AIMS: Localised acidification from immune cell infiltration and heightened glycolysis contributes to colitis pathology by activating acid-sensing receptors such as G protein-coupled receptor 68 (GPR68), a proton-sensing G protein-coupled receptor (GPCR) expressed on immune and stromal cells. Single-cell RNA sequencing (RNA-seq) analysis revealed GPR68 is also expressed in colonic sensory neurons, prompting us to investigate its role in acid-induced colonic nociception. METHODS: mice, supported by pharmacological studies using Ogerin (a GPR68 positive allosteric modulator) and Ogremorphin (a GPR68 antagonist). RESULTS: mice highlighting the involvement of divergent proton-dependent cellular signaling cascades. CONCLUSIONS: These findings identify GPR68 as a key mediator of acid-induced colonic nociception and highlight its potential as a therapeutic target for the treatment of pain in colitis.
Paine et al. (Wed,) studied this question.