Recent advances in acid sensing by G protein coupled receptors

Changes in extracellular proton concentrations occur in a variety of tissues over a range of timescales under physiological conditions and also accompany virtually all pathologies, notably cancers, stroke, inflammation and trauma. Proton-activated, G protein coupled receptors are already partially active at physiological extracellular proton concentrations and their activity increases with rising proton concentrations. Their ability to monitor and report changes in extracellular proton concentrations and hence extracellular pH appears to be involved in a variety of processes, and it is likely to mirror and in some cases promote disease progression. Unsurprisingly, therefore, these pH-sensing receptors (pHR) receive increasing attention from researchers working in an expanding range of research areas, from cellular neurophysiology to systemic inflammatory processes. This review is looking at progress made in the field of pHRs over the past few years and also highlights outstanding issues.