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

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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 Family	Receptor	Species	Parental	Stable Cell Lines	Division-Arrested Cells	Membranes
Proton-Sensing Receptors	GPR4	human	HEK293T	C1100	DC1100	MC1100
	GPR4	human	HEK293T	CA1100	DCA1100	MCA1100
	GPR65	human	HEK293T	C1121	DC1121	MC1121
	GPR65	human	HEK293T	CA1121	DCA1121	MCA1121
	GPR65	human	HEK293T	C1121a	DC1121a	MC1121a
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP20	DC1121-CSP20	MC1121-CSP20
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP23	DC1121-CSP23	MC1121-CSP23
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP30	DC1121-CSP30	MC1121-CSP30
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP36	DC1121-CSP36	MC1121-CSP36
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP38	DC1121-CSP38	MC1121-CSP38
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP44	DC1121-CSP44	MC1121-CSP44
	GPR65	human	Mia-Pa-Ca-2	C1121-CSP75	DC1121-CSP75	MC1121-CSP75
	GPR68	human	HEK293T	C1123	DC1123	MC1123
	GPR68	human	HEK293T	CA1123	DCA1123	MCA1123
	GPR132	human	HEK293T	CA1066	DCA1066	MCA1066