ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- LPAR6 Inhibits the Progression of Hepatocellular Carcinoma (HCC) by Suppressing the Nuclear Translocation of YAP/TAZ.International journal of molecular sciences · 2025Article
- Intracellular TAS2Rs act as a gatekeeper for the excretion of harmful substances via ABCB1 in keratinocytes.FASEB bioAdvances · 2024Article
- Article
- Purinergic signaling during Marek's disease in chickens.Scientific reports · 2023Article
- Review
- [Research progress on the biological regulatory function of lysophosphatidic acid in bone tissue cells].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2020Review
- Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases.Journal of Cancer · 2020Review
- Review
- Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside.Cancers · 2019Review
- Lysophosphatidic acid-induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4.The Journal of clinical investigation · 2019Article
- Production of extracellular lysophosphatidic acid in the regulation of adipocyte functions and liver fibrosis.World journal of gastroenterology · 2018Review
- Lysophosphatidic acid receptor, LPABiochemical and biophysical research communications · 2018Article
- Article
- Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development.Mediators of inflammation · 2017Review
- Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo.Journal of biomedical research · 2016Review
- Lysophosphatidic acid receptors LPA4 and LPA6 differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes.International immunology · 2016Article
- G-Protein-Coupled Lysophosphatidic Acid Receptors and Their Regulation of AKT Signaling.International journal of molecular sciences · 2016Review
- Lysophospholipid receptor nomenclature review: IUPHAR Review 8.British journal of pharmacology · 2014Review
- LPA receptor signaling: pharmacology, physiology, and pathophysiology.Journal of lipid research · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
P2Y5 is a G protein-coupled receptor that binds and is activated by lysophosphatidic acid (LPA). We determined that P2Y5 transcript is expressed along the intestinal mucosa and investigated the intracellular pathways induced by P2Y5 activation, which could contribute to LPA effects on intestinal cell adhesion. P2Y5 heterologously expressed in CHO and small intestinal hBRIE 380i cells was activated by LPA resulting in an increase in intracellular calcium ([Ca(2+)](i)) when the cells concurrently expressed G(alpha)(Delta6qi5myr). P2Y5 activation also increased the phosphorylation of ERK1/2 that was sensitive to pertussis toxin. Together these indicate that P2Y5 activation by LPA induces an increase in [Ca(2+)](i) and ERK1/2 phosphorylation through G(alpha)(i). We discovered that P2Y5 was activated by farnesyl pyrophosphate (FPP) without a detectable change in [Ca(2+)](i). The activation of P2Y5 by LPA or FPP induced the activity of a serum response element (SRE)-linked luciferase reporter that was inhibited by the RGS domain of p115RhoGEF, C3 exotoxin, and Y-27632, suggesting the involvement of G(alpha)(12/13), Rho GTPase, and ROCK, respectively. However, only LPA-mediated induction of SRE reporter activity was sensitive to inhibitors targeting p38 MAPK, PI3K, PLC, and PKC. In addition, only LPA transactivated the epidermal growth factor receptor, leading to an induction of ERK1/2 phosphorylation. These observations correlate with our subsequent finding that P2Y5 activation by LPA, and not FPP, reduced intestinal cell adhesion. This study elucidates a mechanism whereby LPA can act as a luminal and/or serosal cue to alter mucosal integrity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.