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 anaphylaxi s are mediated by submucosal neurons, as are the antisecretory actions of o pioid antidiarrheal medications. We tested the hypothesis that the selectiv e delta-opioid receptor agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) alte rs anaphylaxis-associated ileal anion secretion in vitro. Sheets of ileal m ucosa with attached submucosa from guinea pigs sensitized to cow's milk wer e mounted in Ussing chambers under short-circuit conditions. Mucosal sheets responded to the serosal application of the milk protein, beta-lactoglobul in, with a rapid rise in transepithelial short-circuit current (Isc); in co ntrast, the egg protein, ovalbumin, was without effect. Pretreatment of tis sues with the neuronal conduction blocker, saxitoxin, or the H-1 histamine receptor antagonist, diphenhydramine, but not the opioid receptor antagonis t, naloxone, significantly reduced mucosal responses to antigen. [D-Pen(2) D-Pen(5)]enkephalin (0.1 mu M, serosal addition) decreased baseline Isc, bu t potentiated mucosal responses to antigen; its effects were abolished in t issues pretreated with naloxone. These results suggest that immediate hyper sensitivity reactions in the guinea pig ileal mucosa are mediated by submuc osal neural circuits that are phasically modulated by both mast cell produc ts and opioids. (C) 1999 Elsevier Science B.V. All rights reserved.