Potentiation of anaphylaxis in guinea pig ileal mucosa by a selective delta-opioid receptor agonist.
Immediate hypersensitivity reactions in the intestinal mucosa evoke active chloride secretion which enhances the elimination of luminal antigens. The prosecretory actions of histamine and other soluble mediators of anaphylaxis are mediated by submucosal neurons, as are the antisecretory actions of opioid antidiarrheal medications. We tested the hypothesis that the selective delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) alters anaphylaxis-associated ileal anion secretion in vitro. Sheets of ileal mucosa with attached submucosa from guinea pigs sensitized to cow's milk were mounted in Ussing chambers under short-circuit conditions. Mucosal sheets responded to the serosal application of the milk protein, beta-lactoglobulin, with a rapid rise in transepithelial short-circuit current (Isc); in contrast, the egg protein, ovalbumin, was without effect. Pretreatment of tissues with the neuronal conduction blocker, saxitoxin, or the H1 histamine receptor antagonist, diphenhydramine, but not the opioid receptor antagonist, naloxone, significantly reduced mucosal responses to antigen. [D-Pen-2, D-Pen5]enkephalin (0.1 microM, serosal addition) decreased baseline Isc, but potentiated mucosal responses to antigen; its effects were abolished in tissues pretreated with naloxone. These results suggest that immediate hypersensitivity reactions in the guinea pig ileal mucosa are mediated by submucosal neural circuits that are phasically modulated by both mast cell products and opioids.
Poonyachoti
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Department of Veterinary Pathobiology, University of Minnesota Academic Health Center, St. Paul 55108-6010, USA.
Brown
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D000700:Analgesics / Q000494:pharmacology*; D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D006224:Cricetinae; D004155:Diphenhydramine / Q000494:pharmacology*; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D007782:Lactoglobulins / Q000494:pharmacology; D008297:Male; D008892:Milk / Q000009:adverse effects; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D012530:Saxitoxin / Q000494:pharmacology
D000700:Analgesics; D018926:Anti-Allergic Agents; D007782:Lactoglobulins; D009292:Narcotic Antagonists; D012530:Saxitoxin; D009270:Naloxone; D020881:Enkephalin, D-Penicillamine (2,5)-; D004155:Diphenhydramine; D010047:Ovalbumin