Relex Pathways Controlling Intestinal Motility

Relex 通路控制肠蠕动

基本信息

批准号：
7898176
负责人：
Terence Keith Smith
金额：
$ 10万
依托单位：
UNIVERSITY OF NEVADA RENO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-20 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7898176
关键词：
Affect Afferent Neurons Anus Automobile Driving Bacteria Calcium Cations Cavia Cells Cercopithecidae Characteristics Clinical Colon Computers Constipation Data Dendrites Distal Electrolytes Enteral Ganglia Human Image Interneurons Interstitial Cell of Cajal Intestinal Motility Intestines Laboratories Large Intestine Length Macaca fascicularis Maps Mediating Modeling Monkeys Motor Motor Neurons Movement Myenteric Plexus Myxoid cyst Nerve Neurons Nitric Oxide Nutrient Oral Pacemakers Pathway interactions Pattern Peristalsis Physiological Potassium Channel Primates Production Recovery Rectum Reflex action Sigmoid colon Small Intestines Smooth Muscle Smooth Muscle Myocytes Stimulus Stretching Submucosa System Techniques Tissues Translations Water base neuromechanism novel postsynaptic public health relevance rectal relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): Functions of the large bowel include the recovery of water and electrolytes from the intestinal lumen and the use of bacteria to digest nutrients. To perform these functions the transit of intraluminal contents through the human colon is slow (=30 hrs) compared to transit through the small intestine (2-4hrs). The mechanisms underlying colonic storage and slow transit have remained elusive. Slow transit constipation (STC) has been associated with colonic elongation and other changes, including an excess production of nitric oxide (NO) in myenteric neurons. In this proposal we show that when the guinea-pig distal colon and rectum are impacted with fecal pellets they are elongated by 160% of their length when empty. Intrinsic reflexes activated by colonic elongation appear to promote storage by slowing fecal pellet evacuation. We provide evidence that colonic elongation activates myenteric mechanosensitive descending (NOS +ve) and ascending (Chat +ve) interneurons that initiate polarized descending inhibitory and ascending excitatory reflexes respectively. The descending inhibitory elongation reflex is dominant; it promotes storage by releasing NO to inhibit other mechanosensory interneurons that drive peristalsis. Elongation sensitive descending and ascending interneurons activated by colonic elongation appear to also project to submucosal ganglia and to the submucosal ICC network that produces slow waves, where they inhibit and excite submucosa neurons and ICC respectively. These stretch sensitive interneurons are unusual, since they also appear to function as sensory neurons and motor neurons. In addition, we have found that the monkey sigmoid colon, which is our translation model, has motor patterns that are similar to those in the guinea-pig colon and responds similarly to elongation. PUBLIC HEALTH RELEVANCE: Slow transit constipation has been associated with colonic elongation and an excess production of nitric oxide. The factors underlying slow transit and accommodation of fecal material along the large bowel are unclear. In this proposal we show that when the isolated large bowel contains fecal material it is normally elongated and propulsion is slowed. Colonic elongation activates intrinsic sensory neurons that release nitric oxide to inhibit nerve circuits driving peristalsis. The elongation associated with an impacted colon is likely a contributing factor in slow transit constipation.

描述（由申请人提供）：大肠的功能包括从肠腔回收水和电解质以及利用细菌消化营养物质。为了执行这些功能，与通过小肠的传输（2-4小时）相比，腔内内容物通过人类结肠的传输较慢（= 30小时）。结肠储存和缓慢运输的机制仍然难以捉摸。慢传输便秘（STC）与结肠伸长和其他变化有关，包括肌间神经元中一氧化氮（NO）的过量产生。在该提案中，我们表明，当豚鼠远端结肠和直肠受到粪便颗粒影响时，它们在空时会被拉长 160% 的长度。结肠伸长激活的内在反射似乎可以通过减慢粪便颗粒的排出来促进储存。我们提供的证据表明，结肠伸长激活肌间机械敏感的下行（NOS + ve）和上行（Chat + ve）中间神经元，分别启动极化的下行抑制性反射和上行兴奋性反射。下行抑制性伸长反射占主导地位；它通过释放一氧化氮来抑制其他驱动蠕动的机械感觉中间神经元来促进储存。由结肠伸长激活的伸长敏感的下降和上升中间神经元似乎也投射到粘膜下神经节和产生慢波的粘膜下ICC网络，在那里它们分别抑制和兴奋粘膜下神经元和ICC。这些拉伸敏感的中间神经元很不寻常，因为它们似乎也起到感觉神经元和运动神经元的作用。此外，我们发现猴子乙状结肠（我们的翻译模型）具有与豚鼠结肠相似的运动模式，并且对伸长的反应也相似。公众健康相关性：慢传输型便秘与结肠伸长和一氧化氮过量产生有关。粪便物质沿大肠缓慢运输和调节的潜在因素尚不清楚。在该提案中，我们表明，当分离的大肠含有粪便物质时，它通常会被拉长并且推进速度会减慢。结肠伸长激活内在感觉神经元，释放一氧化氮，抑制驱动蠕动的神经回路。与受影响的结肠相关的伸长可能是慢传输型便秘的一个促成因素。