NEURAL CONTROL OF LARGE INTESTINAL MUCOSA

腹泻是与食物过敏有关的症状之一，寄生虫 感染和炎症性肠病。肥大细胞中的组胺 在这些疾病的发病机制中牵连的多种媒介之一 疾病。总体目标是检查通过哪些机制 组胺介导大鼠脑内协调的分泌和收缩行为 豚鼠结肠。第一个目标针对的是传出路径 粘膜下神经丛介导组胺诱导的周期性分泌 正常的动物。粘膜下层/粘膜准备将在助熔剂中建立 用于记录反射离子的短路电流的电离室 运输。研究将确定黏膜下神经元的类型 有组胺H2受体，测试H3受体是否调节 神经递质释放，并确定胆碱能或VIP 分泌运动神经元是诱导周期性分泌所必需的。神经 途径将通过药理分析，释放~3H- 乙酰胆碱和血管活性肠肽，细胞内电生理记录和 注射技术和免疫组织化学染色方法。这个 第二个目标是确定外在或内在的神经反射 调节周期性分泌和收缩行为的通路 正常动物体内的组胺。对于这些研究，整个厚度段 将被设置在磁通室中。肌肉张力，从拉伤中记录 缝合到浆膜表面的量规换能器将被确定 与离子传输同时进行。这些研究将表明 周期性收缩依赖于周期性分泌的速度， 粘膜下层/粘膜与肌肉之间是否有完整的神经通路 是协调功能所必需的，以及这些通路是否 内在的或外在的起源的神经反射通路的协调 周期性分泌物和肌肉收缩将通过化学方法进行评估。 辣椒素消融，外源性神经通路外科消融 和药理拮抗作用。第三个目标是确定是否 肥大细胞内源性组胺引起协调循环 牛乳致敏豚鼠的分泌和收缩 抗原，β-乳球蛋白。这些研究有望提供 对导致神经免疫信号改变的重要见解 与炎症性疾病相关的分泌状态。

Diarrhea is one of the symptoms associated with food allergies, parasitic infections and inflammatory bowel disease. Histamine from mast cells is one of multiple mediators implicated in the pathogenesis of these diseases. The overall goal is to examine the mechanisms by which histamine mediates coordinated secretory and contractile behavior in the colon of guinea pigs. The first aim addresses the efferent pathways in the submucous plexus that mediate histamine-evoked cyclical secretion in normal animals. Submucosa/mucosa preparations will be set up in flux chambers for recording short-circuit current which reflects ion transport. Studies will identify the types of submucous neurons that have histamine H2 receptors, test whether H3 receptors modulate neurotransmitter release, and determine whether cholinergic or VIP secretomotor neurons are necessary to induce cyclical secretion. Neural pathways will be identified by pharmacological analysis, release of 3H- acetylcholine and VIP, intracellular electrophysiologic recording and injection techniques and immunohistochemical staining methods. The second aim is to determine if extrinsic or intrinsic neural reflex pathways coordinate cyclical secretory and contractile behavior to histamine in normal animals. For these studies whole thickness segments will be set up in flux chambers. Muscle tension, recorded from a strain gauge transducer sutured to the serosal surface, will be determined simultaneously with ion transport. These studies will show whether cyclical contraction is dependent on the rate of cyclical secretion, whether intact neural pathways between the submucosa/mucosa and muscle are necessary for coordination of function and whether these pathways are of intrinsic or extrinsic origin. Neural reflex pathways coordinating cyclical secretion and muscle contraction will be assessed by chemical ablation with capsaicin, surgical ablation of extrinsic neural pathways and pharmacological antagonism. The third aim is to determine whether endogenous histamine from mast cells evokes coordinated cyclical secretion and contraction in guinea pigs sensitized to the bovine milk antigen, beta-lactoglobulin. These studies are expected to provide important insights into neuro-immune signals that result in altered secretory states associated with inflammatory diseases.