A role for phospholipid-derived inflammatory mediators in intestinal anaphylaxis in the rat

This study investigated the role of phospholipid-derived inflammatory mediators in electrolyte transport in the normal rat jejunum and during intestinal anaphylaxis to a food protein in a rat model. In a standard Ussing chamber preparation, the leukotrienes (LTs) C4 and D4 both significantly stimulated an increase in short-circuit current in a concentration-dependent manner. The responses to both LTC4 and LTD4 were significantly reduced by the LTD4 receptor antagonist, MK-571. The 5-lipoxygenase products, LTB4, 5-hydroxyeicosatetraenoic acid and 5-hydroperoxyeicosatetraenoic acid did not significantly alter short-circuit current. The thromboxane mimetic, U-46619, had a small, but significant stimulatory effect on short-circuit current. Platelet-activating factor (PAF) caused a significant, concentration-dependent increase in short-circuit current, with effects at concentrations as low as 2 nM and with a maximum effect of 69 +/- 14 microA/cm2. The stimulatory effect of 0.2 microM PAF was significantly reduced by the PAF receptor antagonist WEB 2086. Exposure of sensitized jejunum to ovalbumin caused a biphasic increase in short-circuit current which was reduced by pretreatment with the 5-lipoxygenase inhibitor, L651,392, and the PAF receptor antagonist, WEB 2086. The response to ovalbumin was not significantly affected by pretreatment of the tissue with the LTD4 receptor antagonist, MK-571, at concentrations which inhibited the responses to exogenous LTC4 and LTD4. The thromboxane/endoperoxide receptor antagonist, L670,596, had no significant effect on the short-circuit current response to ovalbumin.(ABSTRACT TRUNCATED AT 250 WORDS)