Neuronal involvement in type 1 hypersensitivity reactions in gut epithelia

1. Using a number of 5-hydroxytryptamine (5-HT)-antagonists we have compared their activity against the chloride-secretory response in guinea-pig ileal and colonic epithelia when challenged with 5-HT or antigen. Guinea-pigs sensitized to beta-lactoglobulin (beta LG) were used throughout; these were obtained by providing animals with cows' milk for drinking. 2. Of methysergide, ketanserin, cyproheptadine and ICS 205-930, only the latter inhibited both the response to 5-HT and to antigen challenge. Methysergide caused a minor, significant effect on 5-HT but not on beta LG responses. Ketanserin had no effect on the responses to 5-HT, but both ketanserin and cyproheptadine inhibited the challenge to beta LG. 3. The data are considered in relation to the current views of receptor subtypes for 5-HT. Some of the reported inhibitors may be non-specific, while we consider there is evidence to support the view that 5-HT3-receptors (neuronal receptors) are involved both in the responses to 5-HT and to antigen challenge. 4. Tetrodotoxin mimicked the effect of ICS 205-930 on both the response to 5-HT and to antigen challenge in sensitized tissues, confirming a neuronal involvement for both types of stimuli.