Enhanced tissue responsiveness in colonic ion transport of cow's milk-sensitized guinea pigs

The effects of leukotriene D4 (LTD4) on ion transport were investigated in submucosa/mucosa colonic segments from guinea pigs sensitized to cow's milk and in age-matched, non-immune animals. Mediators released from mast cells in immune animals challenged with beta-lactoglobulin evoked an increase in short-circuit current that was reduced by SK&F 102922, a peptidoleukotriene antagonist. Serosal addition of LTD4 (0.15-1 microM) evoked a concentration-dependent, bumetanide-sensitive increase in short-circuit current which was greater in immune than non-immune controls. In the absence of ongoing neural activity, 1 microM LTD4 evoked an 8-20 microA/cm2 increase in short-circuit current which was increased 8-13-fold when ongoing neural activity was present. In tissues with ongoing activity, the response to 0.15 microM LTD4 was reduced by SK&F 102922, tetrodotoxin and atropine. LTD4 enhanced the responsiveness of the tissue to carbachol by a factor of two, but did not affect responses of T84 colonic epithelial cell monolayers to this agent. These results show enhanced secretory function for LTD4 in animals with allergy to cow's milk. They suggest that the level of ongoing neural activity in the enteric neural microcircuits is one of the major determinants of colonic secretory capacity.