Transport abnormalities during intestinal anaphylaxis in the rat: Effect of antiallergic agents

Abstract

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 μg of egg albumin plus alum had specific IgE serum titers ⩾ 1:64; control rats had no measurable IgE antibodies. Net fluxes of Na +, Cl −, and H 2O 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 × 10 −4 mol/L) failed to prevent mucosal mast cell degranulation as evidenced by histamine release or the decrease in absorption of H 2O, 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, H 1, diphenhydramine, or H 2, 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.