GPR68, also known as OGR1 (Ovarian Cancer G-Protein Coupled Receptor 1), is a proton-sensing G-protein coupled receptor that plays important roles in cellular pH homeostasis and stress responses. As a pH sensor in the brain, GPR68 is activated by extracellular acidosis that occurs during neuroinflammation, ischemia, and neurodegeneration, making it a potential therapeutic target for neurodegenerative diseases. [@lp2018]
GPR68 Biology
GPR68 is encoded by the [GPR68](/genes/gpr68) gene and belongs to the proton-sensing GPCR family (including GPR4, GPR65, GPR132). Key features include:
GPR68, also known as OGR1 (Ovarian Cancer G-Protein Coupled Receptor 1), is a proton-sensing G-protein coupled receptor that plays important roles in cellular pH homeostasis and stress responses. As a pH sensor in the brain, GPR68 is activated by extracellular acidosis that occurs during neuroinflammation, ischemia, and neurodegeneration, making it a potential therapeutic target for neurodegenerative diseases. [@lp2018]
GPR68 Biology
GPR68 is encoded by the [GPR68](/genes/gpr68) gene and belongs to the proton-sensing GPCR family (including GPR4, GPR65, GPR132). Key features include:
pH-Sensitive: Activated by extracellular acidosis (optimal pH ~6.5)
Tissue Distribution: Highest in brain, also in bone, kidney, heart
GPR68 functions as a molecular sensor of tissue acidosis, a common feature of neuroinflammation and ischemic injury. [@mj2020]
Mechanism of Action
GPR68 modulators work through acid-sensing and pro-survival signaling:
Mermaid diagram (expand to render)
Key Mechanisms
Acid-Sensing Neuroprotection: In acidic environments characteristic of neuroinflammation and ischemia, GPR68 activation triggers pro-survival signaling through Ca²⁺ release and PKC activation. [@lp2018]
Calcium Signaling: Gq-mediated IP3 production leads to ER Ca²⁺ release, activating calmodulin-dependent survival pathways.