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

• Published in: British journal of pharmacology 2009-01, Vol.147 (7), p.707-713
• Main Authors: Kay, Linda J, Yeo, Wilfred W, Peachell, Peter T
• Format: Article
• Language: English
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706664

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. 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. The DP agonist PGD 2 , the FP agonist PGF 2 α , the IP agonist iloprost and the TP agonist U‐46619 were ineffective inhibitors of IgE‐mediated histamine release from mast cells. PGE 2 induced a concentration‐dependent increase in intracellular cAMP levels in mast cells. 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 (p K B , 5.6±0.1) caused a modest rightward shift in the PGE 2 concentration–response curve, whereas AH23848 was ineffective. 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. Collectively, these data suggest that PGE 2 mediates effects on human lung mast cells by interacting with EP 2 receptors. British Journal of Pharmacology (2006) 147 , 707–713. doi: 10.1038/sj.bjp.0706664