Transport abnormalities during intestinal anaphylaxis in the rat: effect of antiallergic agents.
Our previous studies demonstrated that rats sensitized to egg albumin had reduced intestinal absorption of water and electrolytes in response to intraluminal antigen. The rapid onset of this effect and reduction in mucosal histamine and numbers of granulated mast cells in the lamina propria suggested a reaginic (IgE) mechanism involving mast cell mediators. In this study we examined the effect of antiallergic agents on the intestinal transport abnormalities in our model. Sensitized rats, 14 days after intraperitoneal injection of 10 micrograms of egg albumin plus alum had specific IgE serum titers greater than or equal to 1:64; control rats had no measurable IgE antibodies. Net fluxes of Na+, Cl-, and H2O were determined by in vivo perfusion during a 1-hour antigen-free period and then a 1-hour antigen period. Sodium cromoglycate, administered intravenously (20 mg/kg) or in the perfusate (5 X 10(-4) mol/L) failed to prevent mucosal mast cell degranulation as evidenced by histamine release or the decrease in absorption of H2O, Na+, and Cl- induced by antigen exposure. In contrast, 10(-3) mol/L of doxantrazole in the perfusate completely inhibited these changes. Histamine receptor antagonists, H1, diphenhydramine, or H2, cimetidine, in perfusates had no effect on the transport abnormalities. Our findings support a role for intestinal mucosal mast cells, but not connective tissue mast cells, in the pathogenesis of the intestinal dysfunction associated with mucosal IgE-mediated reactions to food proteins and suggest that mast cell mediators other than histamine are involved.
Perdue
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Gall
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D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones
D006634:Histamine H1 Antagonists; D013892:Thioxanthenes; D044004:Xanthones; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; D004205:Cromolyn Sodium; C010134:doxantrazole