Prostaglandin as a target molecule for pharmacotherapy of allergic inflammatory diseases.
The purpose of this review is to summarize the role of prostaglandins (PGs) in allergic inflammation and to know the value of PGs, as a target molecule for an anti-allergic drug. PGD(2) is the major PG produced by the cyclooxygenase pathway in mast cells. Our and others findings indicate that PGD(2) is one of the potent allergic inflammatory mediators and must be a target molecule of anti-allergic agent. From our data, one of PGD(2) receptor antagonists show clear inhibition of airway hypersensitivity caused by allergic reaction. Concerning the role of PGE(2) in allergic inflammation, conflicting results have been reported. Many experimental data suggest an individual role of each PGE(2) receptor, EP(1), EP(2), EP(3) and EP(4) in allergic reaction. Our results indicate the protective action of PGE(2) on allergic reaction via EP(3). In addition, one of EP(3) agonists clearly inhibits the allergic airway inflammation. These findings indicate the value of EP(3) agonists as an anti-allergic agent. In addition, some investigators including us reported that PGI(2) plays an important role for the protection of the onset of allergic reaction. However, the efficacy of PGI(2) analogue as an anti-allergic agent is not yet fully investigated. Finally, the role of thromboxane A(2) (TxA(2)) in allergic reaction is discussed. Our experimental results suggest a different participation of TxA(2) in allergic reaction of airway and skin. In this review, the role of PGs in allergic inflammation is summarized and the value of PGs as a target molecule for developing a new anti-allergic agent will be discussed.
Nagai
Hiroichi
H
Department of Clinical Pharmacology, Gifu Pharmaceutical University, Gifu, Japan. nagai@gifu-pu.ac.jp
D000818:Animals; D018926:Anti-Allergic Agents / Q000276:immunology* / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D011453:Prostaglandins / Q000276:immunology*; D011971:Receptors, Immunologic / Q000819:agonists / Q000276:immunology; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000276:immunology; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000276:immunology; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013928:Thromboxane A2 / Q000276:immunology
D018926:Anti-Allergic Agents; C545647:PTGER3 protein, human; D011453:Prostaglandins; C545648:Ptger3 protein, mouse; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013928:Thromboxane A2; C036293:prostaglandin D2 receptor