The role of different cyclooxygenase (COX) metabolites released after antigen exposure has been difficult to assess due to simultaneous release of dominant constrictors such as histamine and cysteinyl-leukotrienes (CysLT). In addition prostaglandin E2 (PGE2) also has a powerful effect on basal tone. The aim was to exclude PGE2, histamine and CysLTs from the antigen-induced contraction to define the possible involvement of remaining COX metabolites. Isometric force was measured in guinea pig trachea after exposure to cumulatively increasing concentrations of ovalbumin (OVA; 0.1 ng/ml to 0.1 mg/ml) in the absence or presence of biosynthesis inhibitors and receptor antagonists. Challenge with OVA induced a concentration-dependent contraction that reached 75% of maximal tissue response. COX-inhibition or a combination of EP1 and EP2 receptor antagonism (ONO-8130 and PF-04418948) completely abolished the tone, resulting in an augmented antigen response. COX inhibition in combination with either antihistamines or antileukotrienes (FLAP inhibitor or CysLT1-2 receptor antagonist) displayed no difference compared to COX inhibition alone. However, a combination of all three classes reduced the contraction to 30%, revealing an unknown contractile component. Exchanging COX inhibition with EP1-2 receptor antagonists together with antihistamines and antileukotrienes could not decrease the contraction more than to 50%. However, when a TP receptor antagonist (SQ-29,548) was further included, the maximal antigen contraction reached 30%, similar as previously, clearly revealing a TP-mediated contractile component. PGE2 primarily regulate the basal tone via EP1 and EP2, whereas prostanoids, such as TXA2 and PGD2, contribute as mediator of the antigen-response by activation of the TP receptor.
Keywords: EP receptor; Eicosanoids; Guinea pig trachea; Organ bath; Ovalbumin; TP receptor.
© 2013 Elsevier B.V. All rights reserved.