Relex Pathways Controlling Intestinal Motility

Relex 通路控制肠蠕动

• 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
• 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

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（由申请方提供）：大肠的功能包括从肠腔中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，与通过小肠的转运（2- 4小时）相比，管腔内内容物通过人结肠的转运是缓慢的（=30小时）。结肠储存和缓慢转运的机制仍然是难以捉摸的。慢传输型便秘（STC）与结肠延长和其他变化有关，包括肌间神经元中过量产生一氧化氮（NO）。在这个建议中，我们表明，当豚鼠远端结肠和直肠与粪便颗粒的影响，他们被拉长了160%的长度时，空的。结肠伸长激活的内在反射似乎通过减缓粪便颗粒排空来促进储存。我们提供的证据表明，结肠伸长激活肌间机械敏感性下降（NOS +VE）和上升（聊天+VE）中间神经元，启动极化下降抑制和上升兴奋性反射分别。下行抑制性伸长反射占主导地位;它通过释放NO来抑制其他驱动伸长的机械感觉中间神经元，从而促进储存。结肠伸长激活的伸长敏感的下行和上行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是不寻常的，因为它们似乎也起感觉神经元和运动神经元的作用。此外，我们还发现，猴子的乙状结肠，也就是我们的翻译模型，具有与豚鼠结肠相似的运动模式，并且对延长的反应也相似。公共卫生相关性：慢传输型便秘与结肠延长和一氧化氮过量产生有关。导致粪便沿着大肠缓慢转运和调节的因素尚不清楚。在这个建议中，我们表明，当孤立的大肠含有粪便物质，它通常是拉长和推进减慢。结肠伸长激活了释放一氧化氮的内在感觉神经元，以抑制驱动结肠炎的神经回路。与受影响的结肠相关的延长可能是慢传输型便秘的一个促成因素。