CONTROL OF COLONIC MOTILITY IN HEALTH AND DISEASE

描述：特发性溃疡病患者的结肠动力异常 结肠炎以及结肠炎的动物模型的特点是 通过抑制节律性相性收缩，降低n音调和 巨大移行性收缩(GMC)的频率增加。这些 运动异常在引起脑血管病症状中起着关键作用。 腹泻、排便急迫和腹部痉挛。蜂窝手机 肌张力、时相收缩和GMCs的产生机制 冒号是未知的。这项建议的第一个目的是调查 特定信号转导通路在声调和声调产生中的作用 刺激结肠的时相收缩。第二个目标是 确定这些信号转导通路是如何由 炎症反应抑制声调和时相收缩。钥匙 胞内信使包括胞内游离钙离子，钙离子外流 将测量细胞内存储IP3、DAG和PKC，以支持 生理和药理观察。膜片钳研究将是 在新鲜分离的细胞和取自 正常和发炎的犬结肠。大量的体内和体外数据是 以帮助解释我们的数据和 将其与临床疾病联系起来。粘膜暴露于乙醇和冰醋酸 酸将被用来引起炎症。运动神经功能异常 这个模型类似于人类溃疡性结肠炎的报道。一个 对不同信号转导途径的理解 产生音调和刺激阶段性收缩可能提供机会 对每种类型的收缩进行单独的调节。在……里面 炎症性肠病和其他形式的肠道炎症 需要选择性地刺激阶段性收缩和音调 尽量减少腹泻、排便急迫和腹部不适。

DESCRIPTION: Abnormal colonic motility in idiopathic human ulcerative colitis as well as in animal models of colonic inflammation is characterized by the suppression of rhythmic phasic contractions, decrease n tone and increase in the frequency of giant migrating contraction (GMCs). These motility abnormalities play a key role in producing the symptoms of diarrhea, urgency of defecation and abdominal cramping. The cellular mechanisms for the generation of tone, phasic contractions and GMCs in the colon are not known. The first aim of this proposal is to investigate the roles of specific signal transduction pathways in the generation of tone and stimulation of phasic contractions in the colon. The second aim is to determine how these signal transduction pathways are modulated by the inflammatory response to suppress the tone and phasic contractions. Key intracellular messengers including cytosolic free Ca2+, Ca2+ efflux from intracellular stores, IP3, DAG and PKC, will be measured to support the physiological and pharmacological observations. Patch clamp studies will be done on freshly dissociated cells and circular muscle strips taken from normal and inflamed canine colon. Extensive in vivo and in vitro data are available from this species to help in the interpretation of our data and relating it to clinical diseases. Mucosal exposure to ethanol and acetic acid will be used to induce inflammation. The motility abnormalities in this model are similar to those reported in human ulcerative colitis. An understanding of the differences n signal transduction pathways that generate tone and stimulate phasic contractions may present the opportunity to regulate each type of contraction separately from the other. In inflammatory bowel disease and other forms of gut inflammation it would be desirable to selectively stimulation phasic contractions and tone to minimize diarrhea, urgency of defecation and abdominal discomfort.