Proton-sensing G protein-coupled receptors
Proton-sensing G protein-coupled receptors are
transmembrane receptors which sense acidic pH and include GPR132 (G2A), GPR4, GPR68 (OGR1) and GPR65 (TDAG8).[2] These G protein-coupled receptors are activated when extracellular pH falls into the range of 6.4-6.8 (typical values are above 7.0). The functional role of the low pH sensitivity of the proton-sensing G protein-coupled receptors is being studied in several tissues where cells respond to conditions of low pH including bone and inflamed tissues. The four known proton-sensing G protein-coupled receptors are Class A receptors in subfamily A15
.
Nociception
mice suggest that those channels do not fully account for acid-induced pain sensation.[4] Proton-sensing G protein-coupled receptors have been shown to be expressed in small-diameter neurons responsible for nociception where they may play a role in acid-induced pain sensation.[5] Acid-sensing neuron-mediated immediate pungent pain has been associated with acid-sensing ion channels.[6]
Other functions
Mice lacking each of the four identified proton-sensing GPCRs have been studied.[7] Results so far suggest that these GPCRs might regulate cell proliferation (immune system cells such as lymphocytes and macrophages), but due to redundancy and expression of multiple proton-sensing GPCRs family members in the same cell, multiple gene knockouts are needed. Results for mice lacking OGR1 suggested a possible role for proton-sensing GPCRs in osteoclasts.