Prostaglandin E2 receptor selective agonists E-prostanoid 2 and E-prostanoid 4 may have therapeutic effects on ovalbumin-induced bronchoconstriction.
BACKGROUND
The pharmacologic actions of prostaglandin E(2) (PGE(2)) are mediated through specific E-prostanoid (EP)-1, EP-2, EP-3, and EP-4 receptors. In this study, we determined which PGE(2) receptor 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 PGE(2) or 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 PGE(2). 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 PGE(2) acts through EP-2 and EP-4 receptors.
Tanaka
Hiroshi
H
Third Department of Internal Medicine, Sapporo Medical University school of Medicine, Japan. tanakah@sapmed.ac.jp
Kanako
Satoshi
S
Abe
Shosaku
S
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D016210:Methacholine Chloride; D008738:Methyl Ethers / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D016085:Bronchoconstrictor Agents; D008738:Methyl Ethers; C121546:ONO AE 248; C461399:ONO-AE1-329; C500045:ONO-DI-004; D018078:Receptors, Prostaglandin E; D014665:Vasodilator Agents; D016210:Methacholine Chloride; C016767:sulprostone; D000527:Alprostadil; D015232:Dinoprostone