In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4.
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.
Nagase
T
T
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Fukuchi
Y
Y
Dallaire
M J
MJ
Martin
J G
JG
Ludwig
M S
MS
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
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