GPR68

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GPR68

A gene on chromosome 14q31 that encodes a proton-sensing receptor involved in pH homeostasis, which mediates its action by association with G proteins, stimulating inositol phosphate production or Ca2+ mobilisation.
References in periodicals archive ?
Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J.
In the present review, we discuss the proton-sensing mechanisms, focusing on proton-sensing ionotropic receptors, such as transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs), and metabotropic ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors (GPCRs), in the airway inflammation and AHR in asthma and respiratory diseases.
Recent studies suggest that OGR1-family GPCRs, including OGR1 (GPR68), GPR4, and T cell-death associated gene 8 (TDAG8 or GPR65), also sense extracellular protons and, thereby, stimulates a variety of cellular activities through several types of G proteins [18-21] (Figure 1).
In ASM cells, OGR1 is expressed at by far the highest levels among proton-sensing gPcRs [35].
The role of OGR1 in AHR is supported by recent findings with RGS2-[38] and RGS5-deficient mice [39].
Knockdown of OGR1 and [G.sub.q] expression with small interfering RNAs inhibited acidification-induced increases in [[Ca.sup.2+].sub.i] and mucin production.
Mouse DCs express OGR1family receptors, including OGR1; the functional expression of OGR1 was confirmed by the extracellular acidic pH- and OGR1-dependent increase in [[[Ca.sup.2+]].sub.i].
The findings of the expression of proton-sensing OGR1 in DC, a critical cell for antigen recognition and its presentation to T cells, and the involvement of OGR1 in the DC migration process [59] suggest participation of OGR1 in the pathophysiology of allergic asthma.
Finally, it should be noted that acidic pH modulates DCs leading to Th1 polarization in humans as described [51], which contrasts with the role of OGR1 in Th2 polarization in mice.
Cough and bronchoconstriction are activated by severe acidic pH of 4 to 5 and are mainly mediated by pH-sensing channels through sensory neurons, although pH-sensing OGR1 on ASM cells may also be involved in the cell constriction.
List of Abbreviations AHR: Airway hyperresponsiveness ASIC: Acid-sensing ion channel ASM: Airway smooth muscle [[[Ca.sup.2+]].sub.i]: Intracellular [Ca.sup.2+] concentration DC: Dendritic cell ERK: Extracellular signal-regulated kinase GPCR: G protein-coupled receptor [G.sub.q]: [G.sub.q] protein [G.sub.s]: [G.sub.s] protein LPS: Lipopolysaccharide OGR1: Ovarian cancer G protein-coupled receptor 1 PI3K: Phosphatidylinositol 3-kinase RGS: Regulator of G protein signaling TDAG8: T cell-death associated gene 8 TNF-[alpha]: Tumor necrosis factor-[alpha] TRPV1: Transient receptor potential vanilloid-1 PKA: Protein kinase A.
Mogi et al., "Extracellular acidification stimulates IL-6 production and [Ca.sup.2+] mobilization through proton-sensing OGR1 receptors in human airway smooth muscle cells," American Journal of Physiology--Lung Cellular and Molecular Physiology, vol.