Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE‐dependent secretion from human lung mast cells. Issue 7 (21st June 2013)

• Record Type: Journal Article
• Authors: Kay, L. J.; Gilbert, M.; Pullen, N.; Skerratt, S.; Farrington, J.; Seward, E. P.; Peachell, P. T.
• Is Part Of: Clinical & experimental allergy. Volume 43:Issue 7(2013:Jul.)
• Page Start: 741
• Page End: 751
• Publication Date: 2013-06-21
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12142
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" id="cea12142-abs-0001"> <title>Summary</title> <sec id="cea12142-sec-0001" sec-type="section"> <title>Background</title> <p>Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) has been shown to inhibit IgE‐dependent histamine release from human lung mast cells. This effect of PGE<sub>2</sub> is believed to be mediated by EP<sub>2</sub> receptors. However, definitive evidence that this is the case has been lacking in the absence of EP<sub>2</sub>‐selective antagonists. Moreover, recent evidence has suggested that PGE<sub>2</sub> activates EP<sub>4</sub> receptors to inhibit respiratory cell function.</p> </sec> <sec id="cea12142-sec-0002" sec-type="section"> <title>Objective</title> <p>The aim of this study was to determine the receptor by which PGE<sub>2</sub> inhibits human lung mast cell responses by using recently developed potent and selective EP<sub>2</sub> and EP<sub>4</sub> receptor antagonists alongside other established EP receptor ligands.</p> </sec> <sec id="cea12142-sec-0003" sec-type="section"> <title>Methods</title> <p>The effects of non‐selective (PGE<sub>2</sub>, misoprostol), EP<sub>2</sub>‐selective (ONO‐AE1‐259, AH13205, butaprost‐free acid) and EP<sub>4</sub>‐selective (L‐902, 688, TCS251) agonists on IgE‐dependent histamine release and cyclic‐AMP generation in mast cells were determined. The effects of EP<sub>2</sub>‐selective (PF‐04418948, PF‐04852946) and EP<sub>4</sub>‐selective (CJ‐042794, L‐161, 982) antagonists on PGE<sub>2</sub> responses of mast cells were studied. The expression of EP receptor subtypes was determined by RT‐PCR.</p> </sec> <sec id="cea12142-sec-0004" sec-type="section"> <title>Results</title> <p>Prostaglandin E<sub>2</sub>, EP<sub>2</sub> agonists and EP<sub>4</sub> agonists inhibited IgE‐dependent histamine release from mast cells. PGE<sub>2</sub> and EP<sub>2</sub> agonists, but not EP<sub>4</sub> agonists, increased cyclic‐AMP levels in mast cells. EP<sub>4</sub>‐selective antagonists did not affect the PGE<sub>2</sub> inhibition of histamine release, whereas EP<sub>2</sub>‐selective antagonists caused rightward shifts in the PGE<sub>2</sub> concentration–response curves. RT‐PCR studies indicated that mast cells expressed EP<sub>2</sub> and EP<sub>4</sub> receptors.</p> </sec> <sec id="cea12142-sec-0005" sec-type="section"> <title>Conclusions and Clinical Relevance</title> <p>Although human lung mast cells may express both EP<sub>2</sub> and EP<sub>4</sub> receptors, the principal mechanism by which PGE<sub>2</sub> inhibits mediator release in mast cells is by activating EP<sub>2</sub> receptors.</p> </sec> </abstract>