Prostaglandin E2Receptor Selective Agonists E-Prostanoid 2 and E-Prostanoid 4 May Have Therapeutic Effects on Ovalbumin-Induced Bronchoconstriction

Background: The pharmacologic actions of prostaglandin E2(PGE2) are mediated through specific E-prostanoid (EP)-1, EP-2, EP-3, and EP-4 receptors. In this study, we determined which PGE2receptor subtype(s) contribute to the prevention of allergen-induced bronchoconstriction.Methods: We assessed the effects of these receptor agonists in ovalbumin (OA)-sensitized guinea pigs. The prostaglandin E receptor-subtype agonists tested were ONO-DI-004 (EP-1), ONO-AE1-259 (EP-2), ONO-AE-248 (EP-3), ONO-AE1-329 (EP-4), and sulprostone (EP-1 and EP-3) [Ono Pharmaceutical Company; Osaka, Japan]. We treated the animals with either PGE2or these agonists 15 min before OA challenge and measured respiratory resistance at 15 min, 1 h, and 3 h.Results: Allergen-induced bronchoconstriction was significantly (p < 0.01) suppressed at doses > 85 nmol/kg of PGE2. The respiratory resistance elevations 15 min after OA challenge were significantly (p < 0.01) suppressed by preadministration of EP-2 and EP-4 agonists, but airway responsiveness to inhaled methacholine did not improve. EP-1, EP-3, or EP-1/EP-3 agonists had no effect on any parameter.Conclusions: These results suggest that inhibition of OA-induced bronchoconstriction by PGE2acts through EP-2 and EP-4 receptors.