title: The investigation into indomethacin-induced potentiation of the contractile response to antigen in ovalbumin-sensitized guinea-pig tracheas.
abstract: In the present study, we investigated the mediators involved in the potentiation of antigen-induced contractions by indomethacin in tracheas isolated from ovalbumin (OA)-sensitized guinea-pigs. Indomethacin-induced potentiation of OA contraction was mimicked by prostaglandin DP/EP(1) /EP(2)  receptor antagonist, AH-6809 but not by phospholipase A(2)  enzyme inhibitor mepacrine. The lipoxygenase inhibitor AA-861 did not affect the contraction response to OA but prevented its potentiation by indomethacin, while the leukotriene receptor antagonist cinalukast inhibited both the OA response and its potentiation. However, the antagonists of platelet-activating factor (PAF) (BN-52021), adenosine (CGS-15943), endothelin ET(A)  and ET(B)  receptors (BQ-123, BQ-788), and the neutral endopeptidase inhibitor phosphoramidon did not alter the OA-induced contraction and its potentiation by indomethacin. Furthermore, capsaicin and neuropeptide receptor NK1, NK2, and NK3 antagonists (L-732128, MEN-10376, and SB-218795, respectively) also did not affect the OA-induced contractions and its potentiation. On the other hand, the 'transient receptor potential vanilloid 1' (TRPV1) antagonist capsazepine inhibited the potentiation response, while it did not alter the OA contraction itself. In conclusion, the potentiation of OA-induced contraction by indomethacin is more likely due to the increase in lipoxygenase products by the shift of arachidonic acid towards lipoxygenase pathway. Because some of the lipoxygenase products are potent vanilloid agonists, the stimulation of TRPV1 receptors besides leukotriene receptors seems to participate in the potentiation of contraction response in sensitized guinea-pig tracheas. PAF, adenosine, endothelins, and the neuropeptides present in the afferent neurons do not contribute to the potentiation of OA-induced contraction by indomethacin.
authors.affiliation: Faculty of Pharmacy, Department of Pharmacology, Hacettepe University, 06100 Ankara, Turkey. turgutb@hacettepe.edu.tr
authors.forename: Turgut Emrah
authors.initials: TE
authors.lastname: Bozkurt
authors.forename: Inci
authors.initials: I
authors.lastname: Sahin-Erdemli
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ilhan
mesh_terms: D000818:Animals; D000941:Antigens / Q000502:physiology*; D016718:Arachidonic Acid / Q000502:physiology; D004357:Drug Synergism; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology*; D008084:Lipoxygenase / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D014132:Trachea / Q000276:immunology / Q000502:physiology*
chemical_list: D000941:Antigens; D016718:Arachidonic Acid; D010047:Ovalbumin; D008084:Lipoxygenase; D007213:Indomethacin