8-Epi-PGF2 alpha, a novel noncyclooxygenase-derived prostaglandin, constricts airways in vitro.

8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane formed via a noncyclooxygenase pathway. We investigated whether 8-epi-PGF2 alpha has any effects on isolated guinea-pig and human airway smooth-muscle tone, and characterized the receptor involved in these effects. Cumulative concentration responses to 8-epi-PGF2 alpha in the absence or presence of prostanoid TP- and EP1-receptors antagonists (ICI 192, 605 and AH 6809, respectively) were compared with the responses to U46619 (a thromboxane A2 mimetic) and PGF2 alpha. 8-epi-PGF2 alpha contracted airway smooth muscle with a rank order of potency of U46619 > PGF alpha > 8-epi-PGF2 alpha for guinea pig and U46619 > 8-epi-PGF2 alpha > PGF2 alpha for human smooth muscle. ICI 192,605 inhibited guinea-pig tracheal contraction produced by U46619 (pA2 = 10.0) with a similar potency to its inhibition of the contraction induced by 8-epi-PGF2 alpha (apparent pKB = 10.2, 10.3), but not that induced by PGF2 alpha (apparent pKB = 6.6). AH 6809 inhibited...