Mechanisms underlying regional differences in gastric compliance in the stomach.

胃顺应性区域差异的机制。

• 批准号: 7884627
• 负责人: Sean M Ward
• 金额: $ 25.15万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884627
• 关键词: Abdominal Pain; Animal Model; Animals; Antral; Area; Calcium; Cells; Dependency; Development; Diabetes Mellitus; Diabetic mouse; Digestion; Disease; Distal; Dyspepsia; Event; Food; Frequencies; Functional disorder; Fundus; Gastric Emptying; Gastroparesis; Generations; Impairment; Ingestion; Interstitial Cell of Cajal; Intramuscular; Lead; Length; Mechanics; Mediating; Molecular; Motor; Motor Activity; Muscle; Nausea; Neurons; Pacemakers; Patients; Physiological; Play; Population; Property; Prostaglandin-Endoperoxide Synthase; Prostaglandins; Pyloric antrum; Relaxation; Research Personnel; Role; Signal Transduction; Site; Smooth Muscle; Smooth Muscle Myocytes; Stomach; Stretching; Symptoms; Tissues; diabetic; diabetic gastroparesis; gastric fundus; novel; pressure; programs; regional difference; relating to nervous system; research study; response; voltage; ward

DESCRIPTION (provided by applicant): Millions of patients with functional dyspepsia and gastroparesis, both idiopathic and that associated with diabetes mellitus, have impaired postprandial gastric meal accommodation and uncoordinated gastric contractions which are often accompanied with symptoms of abdominal pain, bloating and nausea. Our hypothesis is that many of these gastric disorders are produced by a disruption in interstitial cells of Cajal (ICC) that are critical for: (i) neurally mediated contractions and relaxations and (ii) rhythmic depolarizations that lead to the electrical and mechanical activities observed in the phasic regions of the stomach. Upon food ingestion the proximal stomach relaxes to accommodate increases in gastric volume without concurrent changes in gastric pressure. The distal stomach responds to gastric distension by increasing phasic motor activity that aids in the breakdown and digestion of gastric contents. The objectives of this proposal are to determine the differences in specific populations of intramuscular ICC (ICC-IM) in the fundus, corpus and antrum and how these differences contribute to the regional diversity in the way the stomach responds to distension following ingestion of a meal. A reductionism approach will be undertaken to compare differences in stretch dependent responses in tissues, isolated muscle bundles and freshly dispersed ICC-IM and smooth muscle cells from three regionally distinct areas of the stomach. The functional roles of ICC- IM will be resolved by examining tissues isolated from animal models that lack ICC-IM in each of these regions and have delayed gastric emptying, similar to that observed in gastroparetic patients. Experiments outlined in this proposal will provide important, novel information on the role of ICC-IM in gastric motor actviity and how differences in the expression of ionic conductances in ICC-IM result in regional diversity in gastric motor activity. The information presented in this proposal is critical towards understanding how specific populations of ICC are involved in gastric accomodation or increased pacemaking activity in the stomach wall following meal ingestion and how the loss of these specalized cells could contribute to lead to impaired gastric accomodation and gastric motor dysfunction in patients suffering from dyspepsia or gastroparesis.

描述（由申请人提供）：数百万患有功能性消化不良和胃轻瘫的患者，无论是特发性的还是与糖尿病相关的，都有餐后胃调节受损和胃收缩不协调的症状，通常伴有腹痛、腹胀和恶心的症状。我们的假设是，许多胃部疾病是由卡哈尔间质细胞 (ICC) 破坏引起的，这些细胞对于以下方面至关重要：(i) 神经介导的收缩和松弛；(ii) 节律性去极化，导致在胃的相位区域观察到的电和机械活动。摄入食物后，近端胃松弛以适应胃容量的增加，而胃压力不会同时变化。远端胃通过增加有助于胃内容物分解和消化的阶段性运动活动来应对胃扩张。该提案的目的是确定眼底、胃体和胃窦肌内 ICC (ICC-IM) 特定人群的差异，以及这些差异如何影响胃对进食后扩张的反应方式的区域多样性。将采用还原论方法来比较来自胃的三个不同区域的组织、分离的肌束和新鲜分散的 ICC-IM 和平滑肌细胞的拉伸依赖性反应的差异。 ICC-IM 的功能作用将通过检查从动物模型中分离的组织来解决，这些动物模型在每个区域都缺乏 ICC-IM，并且胃排空延迟，类似于在胃轻瘫患者中观察到的情况。本提案中概述的实验将为 ICC-IM 在胃运动活动中的作用以及 ICC-IM 中离子电导表达的差异如何导致胃运动活动的区域多样性提供重要的新颖信息。该提案中提供的信息对于了解特定 ICC 群体如何参与胃调节或进食后胃壁起搏活动的增加以及这些特殊细胞的损失如何导致消化不良或胃轻瘫患者的胃调节受损和胃运动功能障碍至关重要。