Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line.
Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.
Barrett
K E
KE
Department of Medicine, University of California, School of Medicine, San Diego 92103.
D000241:Adenosine / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004848:Epithelium / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008407:Mast Cells / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D002712:Chlorides; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D000242:Cyclic AMP; D000241:Adenosine