Proton-Sensing GPCR Family Subtypes and Products

What Are Proton-Sensing Receptors?

Proton-sensing receptors are a family of G protein-coupled receptors (GPCRs) comprised of four receptor subtypes: GPR4, GPR65, GPR68, and GPR132. These receptors are sensitive to extracellular pH levels, and are involved in acid-induced nociceptive pain. Research has also shown a potential role in the regulation of immune system cell proliferation.

Proton-Sensing Receptor Information

Clickable Text Interaction

GPR4

GPR65

GPR68

GPR132

The GPR4 is family of proton-sensing G protein-coupled receptors (GPCRs) and has recently been identified as novel pH sensors. GPR4 sense extracellular protons through histidine residues of the receptors and are coupled to G-proteins to stimulate intracellular signaling pathways. This receptor is expressed in vascular endothelial and smooth muscle cells, as well in a wide range of tissues such as the lung, kidney, heart, and liver. GPR4, upon activation by acidic pH stimulates the Gs/cyclic adenosine monophosphate (cAMP) signaling pathway in endothelial cells and regulatesmicro vessel growth.

GPR65 also known as T cell death-associated gene 8 (TDAG8) is a proton-sensing GPCR and plays a major role in pH homeostasis. This receptor is primarily expressed in lymphoid tissues (spleen, thymus, leukocytes and lymph nodes) and cancer tissues. The major function of this receptor is to reduce immune-mediated inflammation by regulating cytokine production from T cells and macrophages.

GPR68, also known as ovarian cancer G-protein-coupled receptor 1 (OGR1), was previously considered a receptor for sphingosylphosphorylcholine. Recent studies revealed that GPR68 is a proton-sensing GPCR that plays a major role in pH homeostasis. The receptor is expressed in the kidney, placenta, heart, lung, brain, spleen, testis, small intestines, and peripheral blood leucocytes. GPR68 stimulates inositol phosphate (IP) production, Ca2+ mobilization, and cAMP accumulation. The receptor is involved in cell-mediated responses to acidosis in the bone, acts as a metastasis suppressor gene in prostate cancer, and is a potential therapeutic target for obstructive lung diseases.

GPR132 (also known as G2A) is a proton-sensing receptor that is broadly expressed in the appendix, lymph nodes and other tissues. It may also be a receptor for oxidized free fatty acids. It appears to play a role in regulating certain cells of the autoimmune system by responding to the extracellular acidification characteristic of tissues suffering from malignant cell growth or inflammation.

Proton-Sensing Cell Lines

Receptor FamilyReceptorSpeciesParentalStable Cell Lines Division-Arrested Cells Membranes
Proton-Sensing ReceptorsGPR4humanHEK293TC1100DC1100MC1100
GPR4humanHEK293TCA1100DCA1100MCA1100
GPR65humanHEK293TC1121DC1121MC1121
GPR65humanHEK293TCA1121DCA1121MCA1121
GPR65humanHEK293TC1121aDC1121aMC1121a
GPR65humanMia-Pa-Ca-2C1121-CSP20DC1121-CSP20MC1121-CSP20
GPR65humanMia-Pa-Ca-2C1121-CSP23DC1121-CSP23MC1121-CSP23
GPR65humanMia-Pa-Ca-2C1121-CSP30DC1121-CSP30MC1121-CSP30
GPR65humanMia-Pa-Ca-2C1121-CSP36DC1121-CSP36MC1121-CSP36
GPR65humanMia-Pa-Ca-2C1121-CSP38DC1121-CSP38MC1121-CSP38
GPR65humanMia-Pa-Ca-2C1121-CSP44DC1121-CSP44MC1121-CSP44
GPR65humanMia-Pa-Ca-2C1121-CSP75DC1121-CSP75MC1121-CSP75
GPR68humanHEK293TC1123DC1123MC1123
GPR68humanHEK293TCA1123DCA1123MCA1123
GPR132humanHEK293TCA1066DCA1066MCA1066

Full Catalog