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）：接受松弛反射[RRR]被认为是协调进食行为与胃功能的最重要的迷走神经反射机制之一。在反射的经典描述中，进食时发生的食道扩张会导致迷走神经介导的松弛和运动抑制。这种反射可以通过实验引发，并被认为可以让胃接受等压的摄入物。然而，最近的报告表明，在进食期间和之后，RRR 一定会有所暂停，甚至“倒置”，因为此时胃传输实际上比禁食期间更快。我们自己的研究表明，在禁食过夜的老鼠中，食管扩张会导致（正如预期的那样）强烈的胃松弛。相反，我们对进食大鼠的观察表明，食管扩张会导致胃张力显着增加。这种由食管扩张引起的与进食相关的胃张力增加在几个小时后逐渐恢复到“纯粹的”胃松弛。这种重要的迷走神经控制反射功能的巨大变化为我们的总体假设提供了基础：迷走神经胃肠控制反射的神经回路是高度动态的，并受到与进食状态相关的因素的调节。我们之前已经证明，外在因素，尤其是胃肠激素，可以直接并显着地调节肠道的迷走神经反射控制。然而，GI激素可以重组对内脏传入输入的反射反应的具体机制尚不清楚。我们提出，肠道激素的一个子集，特别是CCK和GLP-1，作用于背侧迷走神经复合体中的神经元，以改变孤核[NTS]中突触前catcholamine受体的可用性。我们进一步提出，受体群体的这种转变对背侧迷走神经复合体的反射神经传递模式具有显着影响。我们将结合神经胃肠病学、神经生理学和免疫组织化学方法来测试这些建议。这些关于调节与进食状态相关的迷走神经反射转换的机制的研究结果也可以帮助解释代谢和激素参数的变化如何作用将脑干中的摄取程序生成电路从“进食”切换到“不进食” “ 状态。