TY - JOUR T1 - Endogenous PGE<sub>2</sub> contributes to antigen-induced contractions of guinea pig trachea JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p1781 AU - Jesper Säfholm AU - Lars-Olaf Cardell AU - Sven-Erik Dahlén AU - Mikael Adner Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p1781.abstract N2 - We have previously shown that PGE2 via EP1 receptors maintains basal tone of guinea pig trachea (GPT). Our aim was to assess if antagonism of PGE2 also affected antigen-induced contractions.Isometric responses to administration of ovalbumin (OVA) were recorded in GPT from guinea pigs sensitized to OVA and expressed as% of the maximal contraction to histamine 100μM. Before challenge with OVA, the selective EP1 (ONO-8130; 10nM) antagonist was given to naïve preparations as well as together with different combinations of inhibitors and antagonists of histamine (mepyramine and metiamide), leukotrienes (zileuton) and prostaonids (indomethacin).As shown previously, inhibition of one or two mediator classes, generally had no significant effects, whereas triple mediator antagonism (antihistamines+zileuton+indomethacin) abolished the response to OVA challenge. However, EP1 antagonism partly reduced the antigen contraction. Moreover, when the EP1 antagonist was given together with antihistamines and zileuton, the response to OVA was abolished (Table 1).View this table:Table 1. Contraction (% max) to highest OVA doseEffect of indomethacin together with antihistamines and anti-leukotrienes confirms that prostanoids mediate part of the antigen-induced contraction. The new finding is that EP1 antagonism mimics the effect of indomethacin. This suggests that PGE2 is the main prostanoid mediating the antigen-induced contractions of GPT, a preparation that is known to respond similarly to human airways where the effects of PGE2 still await complete delineation. ER -