Anti-immunoglobulin E-stimulated ion transport in human large and small intestine
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BACKGROUND: Mast-cell regulation of intestinal ion transport, previously shown in animals and cultured cells, was examined in surgically resected human bowel in this study. METHODS: Changes in short-circuit current (Isc) in response to rabbit anti-human immunoglobulin (Ig) E or control serum, histamine, and electrical stimulation were measured in muscle-stripped, noninflamed segments of intestine mounted in Ussing chambers. Chloride-free buffer, pyrilamine, piroxicam, sodium cromoglycate, and tetrodotoxin were examined for their effect on Isc responses to these stimuli. RESULTS: Within 1-2 minutes of adding anti-IgE serum, a specific monophasic rise in Isc (peaking at 7-10 minutes) was observed in large and small intestine. This response was reduced approximately 80% in chloride-free buffer and inhibited by the histamine1-receptor antagonist, pyrilamine, and the cyclo-oxygenase inhibitor, piroxicam, implicating histamine and prostaglandins as mediators of the ion transport changes. The mast-cell stabilizer, sodium cromoglycate, reduced anti-IgE responses in the small, but not large, intestine. Approximately 50% inhibition of anti-IgE responses in colon by the neurotoxin, tetrodotoxin, indicated that nerves were involved. CONCLUSIONS: These results suggest that activation of mast cells releases mediators that stimulate intestinal ion transport through direct epithelial action and via nerves. This study provides important evidence that immunoregulation of intestinal ion transport does occur in humans.
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