Proton-sensing G protein-coupled receptors are

transmembrane receptors Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...

which sense acidic pH and include

GPR132 G protein coupled receptor 132, also termed G2A, is classified as a member of the proton sensing G protein coupled receptor (GPR) subfamily. Like other members of this subfamily, i.e. GPR4, GPR68 (OGR1), and GPR65 (TDAG8), G2A is a G protein c ...

(G2A),

GPR4 G-protein coupled receptor 4 is a protein that in humans is encoded by the ''GPR4'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' ...

, GPR68 (OGR1) and GPR65 (TDAG8). These

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s are activated when

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

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 A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

and

inflamed Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...

tissues. The four known proton-sensing G protein-coupled receptors are Class A receptors in subfamily A15.

Nociception

Pain sensation can be initiated by

nociceptor A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...

cells that are

sensory neuron Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cel ...

s with cell bodies located in the

dorsal root ganglia A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the dorsal ...

. Some nociceptors respond to low pH and the pH-sensitive amiloride-sensitive cation channel 3 has been described as a modulator of acid-induced pain sensation. However, results with amiloride-sensitive cation channel 3 gene knockout mice suggest that those channels do not fully account for acid-induced pain sensation. 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. Acid-sensing neuron-mediated immediate pungent pain has been associated with acid-sensing ion channels.

Other functions

Mice lacking each of the four identified proton-sensing GPCRs have been studied. Results so far suggest that these GPCRs might regulate cell proliferation (immune system cells such as

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s 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

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

References

{{G protein-coupled receptors G protein-coupled receptors