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Prostaglandin E 2 activates EP 2 receptors to inhibit human lung mast cell degranulation

Journal Article


Abstract


  • 1. The prostanoid, PGE 2, is known to inhibit human lung mast cell activity. The aim of the present study was to characterize the EP receptor that mediates this effect. 2. PGE 2 (pEC 50, 5.8±0.1) inhibited the IgE-mediated release of histamine from mast cells in a concentration-dependent manner. Alternative EP receptor agonists were studied. The EP 2-selective agonist, butaprost (pEC 50, 5.2±0.2), was an effective inhibitor of mediator release whereas the EP 1/EP 3 receptor agonist, sulprostone, and the EP 1-selective agonist, 17-phenyl-trinor-PGE 2, were ineffective. 3. The DP agonist PGD 2, the FP agonist PGF 2α, the IP agonist iloprost and the TP agonist U-46619 were ineffective inhibitors of IgE-mediated histamine release from mast cells. 4. PGE 2 induced a concentration-dependent increase in intracellular cAMP levels in mast cells. 5. The effects of the EP 1/EP 2 receptor antagonist, AH6809, and the EP 4 receptor antagonist, AH23848, on the PGE 2-mediated inhibition of histamine release were determined. AH6809 (pK B, 5.6±0.1) caused a modest rightward shift in the PGE 2 concentration-response curve, whereas AH23848 was ineffective. 6. Long-term (24 h) incubation of mast cells with either PGE 2 or butaprost (EP 2 agonist), but not sulprostone (EP 1/EP 3 agonist), caused a significant reduction in the subsequent ability of PGE 2 to inhibit histamine release. 7. Collectively, these data suggest that PGE 2 mediates effects on human lung mast cells by interacting with EP 2 receptors. © 2006 Nature Publishing Group All rights reserved.

Publication Date


  • 2006

Citation


  • Kay, L. J., Yeo, W. W., & Peachell, P. T. (2006). Prostaglandin E 2 activates EP 2 receptors to inhibit human lung mast cell degranulation. British Journal of Pharmacology, 147(7), 707-713. doi:10.1038/sj.bjp.0706664

Scopus Eid


  • 2-s2.0-33645553017

Start Page


  • 707

End Page


  • 713

Volume


  • 147

Issue


  • 7

Abstract


  • 1. The prostanoid, PGE 2, is known to inhibit human lung mast cell activity. The aim of the present study was to characterize the EP receptor that mediates this effect. 2. PGE 2 (pEC 50, 5.8±0.1) inhibited the IgE-mediated release of histamine from mast cells in a concentration-dependent manner. Alternative EP receptor agonists were studied. The EP 2-selective agonist, butaprost (pEC 50, 5.2±0.2), was an effective inhibitor of mediator release whereas the EP 1/EP 3 receptor agonist, sulprostone, and the EP 1-selective agonist, 17-phenyl-trinor-PGE 2, were ineffective. 3. The DP agonist PGD 2, the FP agonist PGF 2α, the IP agonist iloprost and the TP agonist U-46619 were ineffective inhibitors of IgE-mediated histamine release from mast cells. 4. PGE 2 induced a concentration-dependent increase in intracellular cAMP levels in mast cells. 5. The effects of the EP 1/EP 2 receptor antagonist, AH6809, and the EP 4 receptor antagonist, AH23848, on the PGE 2-mediated inhibition of histamine release were determined. AH6809 (pK B, 5.6±0.1) caused a modest rightward shift in the PGE 2 concentration-response curve, whereas AH23848 was ineffective. 6. Long-term (24 h) incubation of mast cells with either PGE 2 or butaprost (EP 2 agonist), but not sulprostone (EP 1/EP 3 agonist), caused a significant reduction in the subsequent ability of PGE 2 to inhibit histamine release. 7. Collectively, these data suggest that PGE 2 mediates effects on human lung mast cells by interacting with EP 2 receptors. © 2006 Nature Publishing Group All rights reserved.

Publication Date


  • 2006

Citation


  • Kay, L. J., Yeo, W. W., & Peachell, P. T. (2006). Prostaglandin E 2 activates EP 2 receptors to inhibit human lung mast cell degranulation. British Journal of Pharmacology, 147(7), 707-713. doi:10.1038/sj.bjp.0706664

Scopus Eid


  • 2-s2.0-33645553017

Start Page


  • 707

End Page


  • 713

Volume


  • 147

Issue


  • 7