Cited by 103Ion Channels and ReceptorsReceptor Mechanisms and SignalingAdenosine and Purinergic Signaling

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Prostaglandin I2 Production and cAMP Accumulation in Response to Acidic Extracellular pH through OGR1 in Human Aortic Smooth Muscle Cells

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Abstract

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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Crossref · 10.1074/jbc.m505287200

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Research works printed but not linked: 3

  1. Leffler, 1999, Am. J. Physiol., 277, H1878
  2. Sato, 1999, Mol. Pharmacol., 55, 126, 10.1124/mol.55.1.126 · DOI
  3. Krampetz, 1991, Am. J. Physiol., 260, L516

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Items 101–103 of 103

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
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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