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)
MacNaughton
W K
WK
Gastrointestinal Research Group, University of Calgary, Alberta, Canada.
Catto-Smith
A G
AG
Gall
D G
DG
D000707:Anaphylaxis / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport; D002227:Carbazoles / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007583:Jejunum / Q000378:metabolism*; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D002227:Carbazoles; D004573:Electrolytes; D006893:Hydroxyeicosatetraenoic Acids; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D010743:Phospholipids; D010972:Platelet Activating Factor; D011422:Propionates; D011804:Quinolines; D013931:Thromboxanes; D014230:Triazoles; C052518:WEB 2086; C061299:L 670596; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C059141:verlukast; C025348:arachidonic acid 5-hydroperoxide; D015232:Dinoprostone