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).
The acidification-induced increase in eosinophil viability and cAMP accumulation was completely lost in the cells isolated from the TDAG8 knockout mice.
TDAG8 is coupled to cAMP signaling pathways and is abundantly expressed in neutrophils.
Thus, TDAG8 is coupled to anti-inflammatory cAMP signaling pathways in macrophages and neutrophils.
have shown that TDAG8 deficiency causes the stimulation of eosinophil apoptosis and, thereby, reduces airway eosinophilia in OVA- and Aspergillus fumigatus-sensitization models of mice in vivo .
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., "TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor," Journal of Biological Chemistry, vol.
Shimizu, "Identification of T cell death-associated gene 8 (TDAG8) as a novel acid sensing g-proteincoupled receptor," Journal of Biological Chemistry, vol.
Tomura et al., "Involvement of protonsensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages," The Journal of Immunology, vol.