Evaluation of Selective Prostaglandin E 2 (PGE 2 ) Receptor Agonists as Therapeutic Agents for the Treatment of Asthma

Abstract

Prostaglandin E 2 (PGE 2 ) 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, PGE 2 also has some proinflammatory properties. PGE 2 acts through four different receptor subtypes (EP1, EP2, EP3, and EP4) that may explain some of PGE 2 ’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 PGE 2 being inactive. Thus, EP3 agonists may lead to a new approach for the treatment of asthma. However, other PGE 2 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.