title: In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4.
abstract: We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the in vitro airway and tissue responses to antigen and the involvement of the potential mediators serotonin (5-HT) and leukotriene D4 (LTD4). We sensitized Brown-Norway rats with ovalbumin (OA) and subsequently challenged bronchial rings and subpleural parenchymal strips with OA in the organ bath. In selected experiments tissues were incubated with methysergide (a 5-HT receptor antagonist), ketanserin (a 5-HT2 receptor antagonist), MK-571 (a LTD4 receptor antagonist), or MK-886 (5-lipoxygenase inhibitor) prior to challenge. Both bronchial rings and parenchymal strips constricted in response to OA. Methysergide and ketanserin completely inhibited OA-induced constriction of bronchial rings. The effect of MK-571 was not significant, whereas MK-886 partially blocked OA-induced bronchial constriction, suggesting a potential role for LTC4 in antigen-induced airway constriction. In parenchymal strips, methysergide, ketanserin, MK-571, and MK-886 all partially inhibited the OA response, whereas the combinations of methysergide and MK-571 or ketanserin and MK-886 completely ablated the response. These data suggest that both bronchial rings and parenchymal strips constrict after OA challenge but that the relative contributions of 5-HT and LTD4 to the allergic response in central airways and parenchymal tissues differ.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Nagase
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: M J
authors.initials: MJ
authors.lastname: Dallaire
authors.forename: J G
authors.initials: JG
authors.lastname: Martin
authors.forename: M S
authors.initials: MS
authors.lastname: Ludwig
mesh_terms: D000403:Airway Resistance / Q000276:immunology / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000276:immunology*; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D017998:Leukotriene D4 / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008784:Methysergide / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology*; D002722:Chlorobenzenes
chemical_list: D007211:Indoles; D007650:Ketanserin; D017998:Leukotriene D4; D016859:Lipoxygenase Inhibitors; D008784:Methysergide; D010047:Ovalbumin; D011422:Propionates; D011804:Quinolines; D011971:Receptors, Immunologic; D012701:Serotonin; C060893:MK-886; D002722:Chlorobenzenes; C059141:verlukast