A LIMITED ROLE FOR LEUKOTRIENES AND PLATELET-ACTIVATING-FACTOR IN FOOD PROTEIN-INDUCED JEJUNAL SMOOTH-MUSCLE CONTRACTION IN SENSITIZED RATS

To determine whether the release of newly formed mediators such as the peptidoleukotrienes and platelet-activating factor might modulate the food protein induced jejunal smooth muscle contraction observed in sensitized rats, Hooded-Lister rats were sensitized by injection of ovalbumin (10-mu-g i.p.) and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally (n = 9) and circularly (n = 9) oriented jejunal segments (mucosa intact) were examined in standard tissue baths in response to antigen, leukotrienes, and platelet-activating factor alone and in the presence of a specific leukotriene receptor antagonist (MK-571), a 5-lipoxygenase inhibitor (L651,392), and a platelet-activating factor receptor antagonist (WEB 2086). Although the responses of control and sensitized tissues to stretch and 10(-4) M bethanechol were similar, only sensitized tissues contracted in response to antigen (1 mg/mL). MK-571 (10(-5) M) reduced or significantly inhibited the contractile response of sensitized longitudinally and circularly oriented tissues to 10(-7) M leukotrienes C4, D4, or E4, but neither L651,392 (10(-4) M) nor MK-571 (10(-5) M) significantly reduced the contractile response of sensitized tissues to antigen challenge. WEB 2086 (10(-4) M) significantly (p < 0.01) reduced the contractile response of sensitized longitudinally and circularly oriented tissues to 10-7 M platelet-activating factor but did not significantly alter the response to antigen in longitudinally (45% of control, p = 0.14) or circularly (118% of control, ns) oriented jejunal smooth muscle. In this model leukotrienes and platelet-activating factor play an insignificant role in modulating food protein induced jejunal smooth muscle contraction in intestinal anaphylaxis.