IN-VITRO AIRWAY AND TISSUE-RESPONSE TO ANTIGEN IN SENSITIZED RATS - ROLE OF SEROTONIN AND LEUKOTRIENE D-4

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norwa y rats. The purpose of the present study was to investigate the in vit ro airway and tissue responses to antigen and the involvement of the p otential mediators serotonin (5-HT) and leukotriene D-4 (LTD(4)). We s ensitized Brown-Norway rats with ovalbumin (OA) and subsequently chall enged bronchial rings and subpleural parenchymal strips with OA in the organ bath. In selected experiments tissues were incubated with methy sergide (a 5-HT receptor antagonist), ketanserin (a 5-HT2 receptor ant agonist), MK-571 (a LTD(4) receptor antagonist), or MK-886 (5-lipoxy-g enase inhibitor) prior to challenge. Both bronchial rings and parenchy mal strips constricted in response to OA. Methysergide and ketanserin completely inhibited OA-induced constriction of bronchial rings. The e ffect of MK-571 was not significant, whereas MK-886 partially blocked OA-induced bronchial constriction, suggesting a potential role for LTC (4) in antigen-induced airway constriction. In parenchymal strips, met hysergide, ketanserin, MK-571, and MK-886 all partially inhibited the OA response, whereas the combinations of methysergide and MK-571 or ke tanserin and MK-886 completely ablated the response. These data sugges t that both bronchial rings and parenchymal strips constrict after OA challenge but-thar the relative contributions of 5-HT and LTD(4) to th e allergic response in central airways and parenchymal tissues differ.