Sleep and Gut Functions : Electrophysiological Actions of Sleep-Related Peptides in the Enteric Nervous System

许多神经肽不仅在大脑中而且在肠道中被确定或提议为神经递质或神经调质，并且被称为脑肠肽。由于已知这些肽中的一些参与控制进食和睡眠，它们可能会提供一些可能的线索，从通过肠道功能进食到睡眠。本研究采用离体豚鼠回肠肌间神经元和盲肠粘膜下神经元的细胞内记录技术，研究了睡眠相关肽对肠神经元电特性和神经节传递的影响，并探讨了睡眠相关肽对睡眠和摄食行为的影响。食欲素A和B均引起一组肌间神经元的膜去极化，并促进ACh或ATP介导的快速EPSP。胃动素去极化一小部分肌间神经元，并抑制快速EPSP。Ghrelin，已知具有结构和功能， ...更多信息 与胃动素相似，具有多种作用，无论是膜去极化还是超极化，并抑制快速EPSP。神经肽Y和神经肽Y相关肽使肌间神经元去极化并抑制快速EPSP。PACAP还引起神经元去极化，抑制粘膜下神经丛的快EPSP。由于这里检查的肽没有改变神经元对乙酰胆碱和ATP的敏感性，食欲素促进，而其他抑制，突触传递，通过增加或减少释放的递质的量。脑肠“睡眠相关”肽，在这里检查，调制豚鼠肠神经系统的神经元活动和突触传递。结论是，这些参与控制肠道功能”可能导致影响摄食行为。培养的初级感觉背根神经节神经元，分离自新生大鼠，当电压钳位在-60 mV时，通过诱导约100 pA的内向电流对食欲素作出反应。第三脑室内灌注食欲素及其相关化合物证明食欲素调节大鼠睡眠。通过增食欲素受体2型增加REM和非REM睡眠来调节觉醒周期。腹腔注射神经肽Y激动剂可增强大鼠的非REM睡眠和摄食行为。第三脑室注入ghrelin和motilin的作用尚在观察中，目前仅从豚鼠回肠和盲肠这两个有限的区域获得的结果来描述睡眠和肠道功能之间的一般关系还为时过早，因为不同动物的消化道不同，反映了它们的摄食行为。少

Many neuropeptides are established or proposed as neurotransmitter or neuromodulators not only in the brain but also in the gut, and termed brain-gut peptides. Since some of these peptides are known to be involved in controlling feeding and sleep, they might provide some possible clues from feeding via gut functions to sleep. In the present project, we investigated their electrophysiological actions on enteric neurons as well as their actions on sleep and feeding behaviors.Intracellular recordings were made in vitro from myenteric neurons of the ileum and submucosal neurons of the cecum of guinea-pigs to examine actions of the sleep-related peptides on neuronal electrical properties and ganglionic transmission. Both of orexin A and B caused membrane depolarizations in a group of myenteric neurons and facilitated fast EPSPs mediated by either ACh or ATP. Motilin depolarized a small population of myenteric neurons and inhibited fast EPSPs. Ghrelin, known to have structural and function-r … More elated similarities to motilin, exerted multiple actions, either membrane depolarization or hyperpolarization, and depressed fast EPSPs. Neuropeptide Y and neuropeptide Y-related peptides depolarized myenteric neurons and inhibited fast EPSPs. PACAP also caused neuronal depolarization and inhibited fast EPSP in the submucosal plexus. Since the peptides examined here did not change the neuronal sensitivity to ACh and ATP, orexins facilitated, whereas others inhibited, synaptic transmission, by increasing or decreasing the amount of released transmitters. The brain-gut "sleep-related" peptides, examined here, modulated neuronal activity and synaptic transmission in the enteric nervous system of guinea-pigs. It is concluded that these are involved in controlling gut functions" possibly leading to affecting feeding behavior.Primary sensory dorsal root ganglion neurons in culture, isolated from neonatal rats, responded to orexin by inducing inward currents of about 100 pA when voltage clamped at -60 mV.Third ventricle intracerebroventricular infusion of orexins and their related compounds demonstrated that orexins regulated the rat sleep-wake cycle by increasing REM and non-REM sleep via orexin receptor type 2. Intraperitoneal application of neuropeptide Y agonist enhanced non-REM sleep and feeding behavior of rats. The actions of ghrelin and motilin infused into third cerebroventricule are now under observations and to be continued.It is premature to describe general relationship between sleep and gut function on the basis of the present results obtained from the limited regions, the ileum and cecum of one animal species, guinea-pig, because the digestive tract is different from animal to animal, reflecting their feeding behavior. Less