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Role of EP 2 and EP 4 receptors in airway microvascular leak induced by prostaglandin E 2
Author(s) -
Jones Victoria C,
Birrell Mark A,
Maher Sarah A,
Griffiths Mark,
Grace Megan,
O'Donnell Valerie B,
Clark Stephen R,
Belvisi Maria G
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13400
Subject(s) - receptor , airway , prostaglandin e , extravasation , inflammation , prostaglandin e2 receptor , lung , medicine , immunology , asthma , chemistry , anesthesia , agonist
Background and Purpose Airway microvascular leak (MVL) involves the extravasation of proteins from post‐capillary venules into surrounding tissue. MVL is a cardinal sign of inflammation and an important feature of airway inflammatory diseases such as asthma. PGE 2 , a product of COX‐mediated metabolism of arachidonic acid, binds to four receptors, termed EP 1–4 . PGE 2 has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE 2 on airway MVL and the receptor/s that mediate this have not been described. Experimental Approach Evans Blue dye was used as a marker of airway MVL, and selective EP receptor agonists and antagonists were used alongside EP receptor‐deficient mice to define the receptor subtype involved. Key Results PGE 2 induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE 2 ‐induced MVL was demonstrated in Ptger2 − / − and Ptger4 − / − mice and in wild‐type mice pretreated simultaneously with EP 2 (PF‐04418948) and EP 4 (ER‐819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE 2 was associated with a rise in MVL; this change was absent in Ptger2 − / − and Ptger4 − / − mice.Conclusions and Implications PGE 2 is a key mediator produced by the lung and has widespread effects according to the EP receptor activated. Airway MVL represents a response to injury and under ‘disease’ conditions is a prominent feature of airway inflammation. The data presented highlight a key role for EP 2 and EP 4 receptors in MVL induced by PGE 2.