Brainstem Esophageal-Gastric Reflexes

脑干食管胃反射

• 批准号: 6911244
• 负责人: Richard C. Rogers
• 金额: $ 32.34万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911244
• 关键词: adrenergic receptor; autonomic reflex; brain stem; cholecystokinin; cyclic AMP; enteric nervous system; esophagus motility /pressure; fasting; gastrointestinal hormones; hormone regulation /control mechanism; immunocytochemistry; incretin hormone; laboratory rat; neural transmission; neurophysiology; neuroregulation; stomach motility /pressure; swallowing; vagus nerve

DESCRIPTION (provided by applicant): The receptive relaxation reflex [RRR] is acknowledged as one of the most important vagal reflex mechanisms coordinating feeding behavior with gastric function. In the classic description of the reflex, distension of the esophagus, as occurs while feeding, causes a vagally-mediated relaxation and suppression of motility. This reflex can be elicited experimentally and is assumed to allow the stomach to accept ingesta isobarically. More recent reports show, however, that the RRR must be some how suspended, or even "inverted" during and after feeding since gastric transit is actually more rapid at these times than during fasting. Our own studies show that in rats fasted overnight, esophageal distention causes (as expected) a powerful gastric relaxation. Conversely, our observations in fed rats show that esophageal distention induces a significant increase in gastric tone. This feeding-related increase in gastric tone induced by esophageal distention gradually reverts back to a "pure" gastric relaxation after few hours. This dramatic change in the function of such an essential vagal control reflex provides the basis for our overarching hypothesis: Neural circuits underlying vago-vagal gastrointestinal control reflexes are highly dynamic and regulated by factors associated with feeding status. We have previously shown that extrinsic factors, especially gastrointestinal hormones, directly and dramatically modulate vago-vagal reflex control of the gut. However, the specific mechanisms by which Gl hormones can reorganize a reflex response to a visceral afferent input are not well understood. We propose that a subset of gut hormones, in particular, CCK and GLP-1, act on neurons in the dorsal vagal complex to alter the availability of presynaptic catcholamine receptors in the solitary nucleus [NTS]. We propose further that this shift in receptor population has a dramatic effect on reflex neurotransmission patterns in the dorsal vagal complex. We will apply a combination of neurogastroenterological, neurophysiological and immunohistochemical methods to test these proposals. Results from these studies on mechanisms regulating the feeding-state-related switching of vago-vagal reflexes could also help explain how changes in metabolic and hormonal parameters can act to switch ingestion program generation circuits in the brainstem from a "feeding" to "not feeding" state.

描述（由申请人提供）：接受的松弛反射[RRR]被公认为是与胃功能协调喂养行为的最重要的迷走色反射机制之一。在对反射的经典描述中，食管的延伸正如进食时发生的那样，引起了模糊的介导的松弛和运动抑制。可以通过实验引起这种反射，并假定允许胃接受INGESTA。然而，最近的报告显示，由于胃交通在这些时间实际上比禁食期间，RRR必须在进食过程中和喂食期间和喂食之后的悬浮速度更快。我们自己的研究表明，在禁食过夜的大鼠中，食管延伸的原因（如预期）是一种强大的胃松弛。相反，我们在联邦大鼠中的观察结果表明，食管延伸会诱导胃张力的显着增加。几个小时后，食管扩张引起的这种与喂养相关的胃张力增加逐渐恢复为“纯”胃松弛。这种基本迷走神经控制反射功能的这种戏剧性变化为我们的总体假设提供了基础：神经胶接种胃肠道反射的基础神经回路反射是高度动态的，并且受喂养状态相关的因素的调节。我们先前已经表明，外在因素，尤其是胃肠道激素，直接和显着调节了肠道的Vago-Vagal反射控制。但是，尚不清楚GL激素可以重新组织对内脏传入输入的反射反应的特定机制。我们提出，肠道激素的一部分，尤其是CCK和GLP-1，作用于背部迷走神经复合物中神经元，以改变孤立核[NTS]中突触前捕醇蛋白受体的可用性。我们进一步提出，这种受体人群的这种转变对背部迷走神经络合物中的反射神经传递模式产生了巨大影响。我们将采用神经胃肠道，神经生理和免疫组织化学方法的结合来测试这些建议。这些有关调节流失式反射的机制的研究的结果还可以帮助解释代谢和激素参数的变化如何作用以将脑干中的摄入程序产生回路从“进食”转换为“不喂食”状态。