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.