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Prostaglandin I2 Production and cAMP Accumulation in Response to Acidic Extracellular pH through OGR1 in Human Aortic Smooth Muscle Cells
Open accessAbstract
Ovarian cancer G-protein-coupled receptor 1 (OGR1) and GPR4 have recently been identified as proton-sensing or extracellular pH-responsive G-protein-coupled receptors stimulating inositol phosphate production and cAMP accumulation, respectively. In the present study, we found that OGR1 and GPR4 mRNAs were expressed in human aortic smooth muscle cells (AoSMCs). Acidic extracellular pH induced inositol phosphate production, a transient increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), and cAMP accumulation in these cells. When small interfering RNAs (siRNAs) targeted for OGR1 and GPR4 were transfected to the cells, the acid-induced inositol phosphate production and [Ca(2+)](i) increase were markedly inhibited by the OGR1 siRNA but not by the GPR4 siRNA. Unexpectedly, the acid-induced cAMP accumulation was also largely inhibited by OGR1 siRNA but only slightly by GPR4 siRNA. Acidic extracellular pH also stimulated prostaglandin I2 (PGI(2)) production, which was again inhibited by OGR1 siRNA. The specific inhibitors for extracellular signal-regulated kinase kinase and cyclooxygenase attenuated the acid-induced PGI(2) production and cAMP accumulation without changes in the inositol phosphate production. A specific inhibitor of phospholipase C also inhibited the acid-induced cAMP accumulation. In conclusion, OGR1 is a major receptor involved in the extracellular acid-induced stimulation of PGI(2) production and cAMP accumulation in AoSMCs. The cAMP accumulation may occur through OGR1-mediated stimulation of the phospholipase C/cyclooxygenase/PGI(2) pathway.
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“Medium acidification during in vitro cell culture can also initiate pro-inflammatory signaling responses in human aortic smooth muscle cells (Tomura et al., 2005) and cells of the human nucleus pulposus (Gilbert et al., 2016).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as Tomura et al., 2005
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2 retracted
Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1
Xu, Y., Zhu, K., Hong, G., Wu, W., Baudhuin, L. M., Xiao, Y.-J., & Damron, D. S. (2000) · Nature Cell Biology · doi:10.1038/35010529 · Cited by 289
RetractedZhu, K., Baudhuin, L. M., Hong, G., Williams, F. S., Cristina, K. L., Kabarowski, J. H. S., Witte, O. N., & Xu, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008057200 · Cited by 242
RetractedThe Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors
Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E. E., Baumruker, T., HIESTAND, P. C., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200176200 · Cited by 1,512
Proton-sensing G-protein-coupled receptors
Ludwig, M., Vanek, M., Guerini, D., Gasser, J. A., Jones, C. E., JUNKER, U., Hofstetter, H., Wolf, R. M., & Seuwen, K. (2003) · Nature · doi:10.1038/nature01905 · Cited by 746
Therapeutic effects of lysophosphatidylcholine in experimental sepsis
Yan, J.-J., JUNG, J., Lee, J.-E., Lee, J.-H., Huh, S., Kim, H., Jung, K. C., Cho, J., Nam, J., Suh, H., et al. (2004) · Nature Medicine · doi:10.1038/nm989 · Cited by 328
TDAG8 Is a Proton-sensing and Psychosine-sensitive G-protein-coupled Receptor
Wang, J.-Q., Kon, J., Mogi, C., Tobo, M., Damirin, A., Sato, K., Komachi, M., Malchinkhuu, E., Murata, N., Kimura, T., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406966200 · Cited by 256
Self-citationG2A Is a Proton-sensing G-protein-coupled Receptor Antagonized by Lysophosphatidylcholine
Murakami, N., Yokomizo, T., Okuno, T., & Shimizu, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406561200 · Cited by 253
Okajima, F. (2002) · Biochimica et Biophysica Acta · doi:10.1016/s1388-1981(02)00147-6 · Cited by 244
Self-citationMice Lacking the Orphan G Protein-Coupled Receptor G2A Develop a Late-Onset Autoimmune Syndrome
Le, L. Q., Kabarowski, J. H. S., Weng, Z., Satterthwaite, A. B., Harvill, E. T., Jensen, E. R., Miller, J. F., & Witte, O. N. (2001) · Immunity · doi:10.1016/s1074-7613(01)00145-5 · Cited by 215
Radu, C. G., Nijagal, A., McLaughlin, J., Wang, L., & Witte, O. N. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409415102 · Cited by 213
Kon, J., Sato, K., Watanabe, T., Tomura, H., Kuwabara, A., Kimura, T., Tamama, K., Ishizuka, T., Murata, N., Kanda, T., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.23940 · Cited by 213
Self-citationIshii, S., Kihara, Y., & Shimizu, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407832200 · Cited by 199
Identification of a Molecular Target of Psychosine and Its Role in Globoid Cell Formation
Im, D., Heise, C. E., Nguyen, T., O’Dowd, B. F., & Lynch, K. R. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.2.429 · Cited by 190
Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A
Yang, L. V., Radu, C. G., Wang, L., Riedinger, M., & Witte, O. N. (2004) · Blood · doi:10.1182/blood-2004-05-1916 · Cited by 179
Yamada, T., Sato, K., Komachi, M., Malchinkhuu, E., Tobo, M., Kimura, T., Kuwabara, A., Yanagita, Y., IKEYA, T., Tanahashi, Y., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308133200 · Cited by 176
Self-citationWalley, K. R., Lewis, T. H., & WOOD, L. D. H. (1990) · Circulation Research · doi:10.1161/01.res.67.3.628 · Cited by 156
A DNA damage and stress inducible G protein-coupled receptor blocks cells in G 2 /M
Weng, Z., Fluckiger, A.-C., Nisitani, S., Wahl, M. I., Le, L. Q., Hunter, C. A., Fernal, A. A., Beau, M. M. L., & Witte, O. N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12334 · Cited by 151
Klemm, D. J., Watson, P. A., Frid, M. G., Dempsey, E. C., Schaack, J. B., Colton, L. A., Nesterova, A., Stenmark, K. R., & Reusch, J. E. B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104769200 · Cited by 139
Sphingosylphosphorylcholine—biological functions and mechanisms of action
zu Heringdorf, D. M. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(02)00154-3 · Cited by 135
Lin, P., & Ye, R. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209101200 · Cited by 132
Bünemann, M., Liliom, K., Brandts, B., Pott, L., Tseng, J., Desiderio, D. M., Sun, G., Miller, D. D., & Tigyi, G. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00937.x · Cited by 122
Hypercapnic Acidosis Activates K ATP Channels in Vascular Smooth Muscles
Wang, X., Wu, J., Li, L., Chen, F., Wang, R., & Jiang, C. L. (2003) · Circulation Research · doi:10.1161/01.res.0000075601.95738.6d · Cited by 118
Identification of Human OGR1, a Novel G Protein-Coupled Receptor That Maps to Chromosome 14
Xu, Y., & Casey, G. (1996) · Genomics · doi:10.1006/geno.1996.0377 · Cited by 109
Quantitative Measurement of Sphingosine 1-Phosphate by Radioreceptor-Binding Assay
Murata, N., Sato, K., Kon, J., Tomura, H., & Okajima, F. (2000) · Analytical Biochemistry · doi:10.1006/abio.2000.4580 · Cited by 107
Self-citationDirect Activation of Cloned KATP Channels by Intracellular Acidosis*
Xu, H.-X., Cui, N., Yang, Z.-J., Wu, J., Giwa, L. R., Abdulkadir, L., Sharma, P., & Jiang, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009631200 · Cited by 95
BATLLE, D. C., Peces, R., LaPointe, M. S., Ye, M., & Daugirdas, J. T. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.264.4.c932 · Cited by 94
Tian, R., Vogel, P., Lassen, N. A., Mulvany, M. J., Andreasen, F., & Aalkjær, C. (1995) · Circulation Research · doi:10.1161/01.res.76.2.269 · Cited by 79
Sato, K., Tomura, H., Igarashi, Y., Ui, M., & Okajima, F. (1999) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)23170-9 · Cited by 71
Self-citationThe G Protein-Coupled Receptor GPR4 Suppresses ERK Activation in a Ligand-Independent Manner
Bektas, M., Barak, L. S., Jolly, P. S., Liu, H., Lynch, K. R., Lacaná, E., Suhr, K., Milstien, S., & Spiegel, S. (2003) · Biochemistry · doi:10.1021/bi035051y · Cited by 69
Coronary Arteriolar Dilation to Acidosis
Ishizaka, H., Gudi, S. R. P., Frangos, J. A., & Kuo, L. (1999) · Circulation · doi:10.1161/01.cir.99.4.558 · Cited by 67
Cloning, Characterization, and Mapping of Human Homolog of Mouse T-Cell Death-Associated Gene
Kyaw, H., Zeng, Z., Su, K., Fan, P., Shell, B. K., CARTER, K. C., & Li, Y. (1998) · DNA and Cell Biology · doi:10.1089/dna.1998.17.493 · Cited by 64
ATP-Sensitive Potassium Channels in the Cerebral Circulation
Rosenblum, W. I. (2003) · Stroke · doi:10.1161/01.str.0000070425.98202.b5 · Cited by 59
Damirin, A., Tomura, H., Komachi, M., Tobo, M., Sato, K., Mogi, C., Nochi, H., Tamoto, K., & Okajima, F. (2004) · Molecular Pharmacology · doi:10.1124/mol.104.004317 · Cited by 56
Self-citationMetabolic pathways and physiological and pathological significances of lysolipid phosphate mediators
Tokumura, A. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20147 · Cited by 53
Lysophosphatidylcholine up-regulates CXCR4 chemokine receptor expression in human CD4 T cells
Han, K. H., Hong, K. H., Ko, J., Rhee, K. S., Hong, M., Kim, J., Kim, Y. H., & Park, S. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1103563 · Cited by 51
Iwasawa, K., Nakajima, T., Hazama, H., Goto, A., Shin, W. S., Toyo‐oka, T., & Omata, M. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.237bh.x · Cited by 48
Hyvelin, J.-M., O'CONNOR, C. M., & McLoughlin, P. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00331.2003 · Cited by 42
Eicosanoid biosynthesis in human cardiovascular disease
FitzGerald, G. A., Catella, F., & Oates, J. A. (1987) · Human Pathology · doi:10.1016/s0046-8177(87)80007-2 · Cited by 42
Hayabuchi, Y., Nakaya, Y., Matsuoka, S., & Kuroda, Y. (1998) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240050665 · Cited by 39
Recent advances in the biochemistry and genetics of sphingolipidoses
Özkara, H. A. (2004) · Brain and Development · doi:10.1016/j.braindev.2004.01.005 · Cited by 33
Antimitogenic effects of vasodilatory prostaglandins in coronary artery smooth muscle cells
Weber, A.-A., Zucker, T.-P., Hasse, A., Bönisch, D., Wittpoth, M., & Schrör, K. (1998) · Basic Research in Cardiology · doi:10.1007/s003950050218 · Cited by 16
Relaxant Responses to Prostaglandin F2α and E2 of Isolated Human Uterine Arteries
Kimura, T., Okamura, T., Yoshida, Y., & Toda, N. (1995) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199508000-00021 · Cited by 15
Flagged first, then by citations
Research works printed but not linked: 3
- Leffler, 1999, Am. J. Physiol., 277, H1878
- Sato, 1999, Mol. Pharmacol., 55, 126, 10.1124/mol.55.1.126 · DOI
- Krampetz, 1991, Am. J. Physiol., 260, L516
Cited by
Sorted by citations
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Lysophospholipid receptors: Signalling, pharmacology and regulation by lysophospholipid metabolism
zu Heringdorf, D. M., & Jakobs, K. H. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.09.026 · Cited by 393
Acidic tumor microenvironment and pH-sensing G protein-coupled receptors
Justus, C. R., Dong, L., & Yang, L. V. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00354 · Cited by 378
Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65
Huang, X.-P., Karpiak, J., Kroeze, W. K., Zhu, H., Chen, X., Moy, S. S., Saddoris, K. A., Nikolova, V. D., Farrell, M. S., Wang, S., et al. (2015) · Nature · doi:10.1038/nature15699 · Cited by 284
Airway smooth muscle in airway reactivity and remodeling: what have we learned?
Prakash, Y. (2013) · American Journal of Physiology - Lung cellular and Molecular Physiology · doi:10.1152/ajplung.00259.2013 · Cited by 207
Metadata
- Authors
- Tomura, H., Wang, J.-Q., Komachi, M., Damirin, A., Mogi, C., Tobo, M., Kon, J., Misawa, N., Sato, K., & Okajima, F.
- Affiliations
- Gunma University (JP)
- Kirin (Japan) (JP)
- Corresponding author
- Tomura, Hideaki
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 280
- Issue
- 41
- Pages
- 34458-34464
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2076643673
- Cited by
- 103
- References
- 42
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 2 · 2017: 2 · 2016: 8 · 2015: 10 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Nakatomi Foundation
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- OGR1, GPR4, proton-sensing G protein-coupled receptor, extracellular acidosis, prostacyclin, cAMP accumulation, inositol phosphate formation, intracellular calcium, aortic smooth muscle cells, phospholipase C, cyclooxygenase, ERK kinase
- MeSH terms
- Cyclic AMP, Aorta, Calcium, Enzyme Inhibitors, Humans, Hydrogen-Ion Concentration, Inositol Phosphates, Type C Phospholipases, Epoprostenol, Transfection, Signal Transduction, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Smooth Muscle, RNA, Small Interfering, Receptors, G-Protein-Coupled
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