Evaluation of selective prostaglandin E2 (PGE2) receptor agonists as therapeutic agents for the treatment of asthma.
Prostaglandin E2 (PGE2) released in asthmatic airways has bronchodilator properties and inhibits allergen-induced bronchoconstriction and release of inflammatory mediators. Although considered as a potential treatment for asthma, PGE2 also has some proinflammatory properties. PGE2 acts through four different receptor subtypes (EP1, EP2, EP3, and EP4) that may explain some of PGE2's diverse effects. In a mouse model of allergic inflammation in which the four receptors were individually deleted, only EP3(-/-) mice showed an enhancement of inflammation, whereas an EP3 agonist was inhibitory, with PGE2 being inactive. Thus, EP3 agonists may lead to a new approach for the treatment of asthma. However, other PGE2 receptor subtypes may also have beneficial effects, and a greater understanding of the signaling pathways of these receptor subtypes will help to clarify the role of these receptors in asthma.
Chung
K F
KF
National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK. f.chung@imperial.ac.uk
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008407:Mast Cells / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D058308:Receptors, Prostaglandin E, EP3 Subtype
D018927:Anti-Asthmatic Agents; D001095:Arachidonic Acids; D008565:Membrane Proteins; C545647:PTGER3 protein, human; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone