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Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2

Jones, Victoria C ; Birrell, Mark A ; Maher, Sarah A ; Griffiths, Mark ; Grace, Megan ; O'Donnell, Valerie B ; Clark, Stephen R ; Belvisi, Maria G

British journal of pharmacology, 2016-03, Vol.173 (6), p.992-1004 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

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Título:
Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2
Autor: Jones, Victoria C ; Birrell, Mark A ; Maher, Sarah A ; Griffiths, Mark ; Grace, Megan ; O'Donnell, Valerie B ; Clark, Stephen R ; Belvisi, Maria G
Assuntos: Allergens ; Animals ; Arachidonic acid ; Asthma ; Asthma - metabolism ; Azetidines - pharmacology ; Benzazepines - pharmacology ; Bronchi - metabolism ; Capillary Permeability ; Dinoprostone - analogs & derivatives ; Dinoprostone - metabolism ; Dinoprostone - pharmacology ; Extravasation ; Guinea Pigs ; Imidazoles - pharmacology ; Inflammation ; Inflammatory diseases ; Lungs ; Male ; Metabolism ; Methyl Ethers - pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microvasculature ; Ovalbumin ; Prostaglandin E2 ; Proteins ; Receptors, Prostaglandin E, EP2 Subtype - agonists ; Receptors, Prostaglandin E, EP2 Subtype - antagonists & inhibitors ; Receptors, Prostaglandin E, EP2 Subtype - genetics ; Receptors, Prostaglandin E, EP2 Subtype - metabolism ; Receptors, Prostaglandin E, EP4 Subtype - agonists ; Receptors, Prostaglandin E, EP4 Subtype - antagonists & inhibitors ; Receptors, Prostaglandin E, EP4 Subtype - genetics ; Receptors, Prostaglandin E, EP4 Subtype - metabolism ; Research Paper ; Research Papers ; Respiratory tract ; Respiratory tract diseases ; Trachea - metabolism
É parte de: British journal of pharmacology, 2016-03, Vol.173 (6), p.992-1004
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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. PGE2, a product of COX‐mediated metabolism of arachidonic acid, binds to four receptors, termed EP1–4. PGE2 has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE2 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 PGE2 induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE2‐induced MVL was demonstrated in Ptger2−/− and Ptger4−/− mice and in wild‐type mice pretreated simultaneously with EP2 (PF‐04418948) and EP4 (ER‐819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE2 was associated with a rise in MVL; this change was absent in Ptger2−/− and Ptger4−/− mice. Conclusions and Implications PGE2 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 EP2 and EP4 receptors in MVL induced by PGE2.
Editor: England: Blackwell Publishing Ltd
Idioma: Inglês

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Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2

Jones, Victoria C ; Birrell, Mark A ; Maher, Sarah A ; Griffiths, Mark ; Grace, Megan ; O'Donnell, Valerie B ; Clark, Stephen R ; Belvisi, Maria G

England: Blackwell Publishing Ltd

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