Prostaglandin I2 Production and cAMP Accumulation in Response to Acidic Extracellular pH through OGR1 in Human Aortic Smooth Muscle Cells
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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 initiate pro-inflammatory signaling responses in human aortic smooth muscle cells and cells of the human nucleus pulposus.
“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
The Results show that acidic medium triggers OGR1-mediated PGI2 production and cAMP accumulation in human aortic smooth muscle cells. But the Discussion characterizes this response as a possible mechanism that counteracts inflammation, not a pro-inflammatory response. The separate nucleus pulposus claim is attributed to Gilbert et al., not to this source. (LLM, conf=0.86)
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- 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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