| Co-Investigator(Kenkyū-buntansha) |
HIRAI Kenji Tokyo Medical and Dental University, Medical Research Institute, Associate Professor, 難治疾患研究所, 助教授 (70156628)
HONDA Kazuki Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Associate Professor, 生体材料工学研究所, 助教授 (70173656)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
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
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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
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