Javed N H, Barrett K E, Wang Y Z, Bidinger J, Cooke H J
Department of Physiology, Ohio State University, Columbus 43210.
Agents Actions. 1994 Mar;41(1-2):25-31. doi: 10.1007/BF01986389.
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.
在对牛奶致敏的豚鼠的结肠黏膜下层/黏膜段以及年龄匹配的非免疫动物中，研究了白三烯D4（LTD4）对离子转运的影响。用β-乳球蛋白攻击免疫动物的肥大细胞释放的介质引起短路电流增加，该增加被肽白三烯拮抗剂SK&F 102922所抑制。浆膜加入LTD4（0.15 - 1微摩尔）引起短路电流浓度依赖性、布美他尼敏感的增加，免疫动物中的增加幅度大于非免疫对照。在没有持续神经活动的情况下，1微摩尔LTD4引起短路电流增加8 - 20微安/平方厘米，当存在持续神经活动时，增加幅度为8 - 13倍。在有持续活动的组织中，SK&F 102922、河豚毒素和阿托品可降低对0.15微摩尔LTD4的反应。LTD4使组织对卡巴胆碱的反应性增强两倍，但不影响T84结肠上皮细胞单层对该药物的反应。这些结果表明，LTD4在对牛奶过敏的动物中分泌功能增强。它们提示，肠神经微回路中持续神经活动的水平是结肠分泌能力的主要决定因素之一。
