| Co-Investigator(Kenkyū-buntansha) |
TAXI Jacques Institute Des Neurosciences, Universite Pierre et Marie CURIE Emeritus Professor, 名誉教授
ANGLADE Philippe Institute Des Neurosciences, Universite Pierre et Marie CURIE Researcher, 研究員
SUZUKI Yuichi University of Shizuoka Associate Professor, 食品科学部, 助教授 (50091707)
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| Research Abstract |
Intestine is quite complex organ due to the heterogeneity of its structure ; the intestine consists of muscle, nerve plexus and mucosa. Extensive networks of nerve fibers are found in the muscle and mucosa in the intestine. Most of these fibers arise from ganglion cells in the myenteric or submucous plexuses. These plexuses regulate the gastrointestinal functions including motility, water and electrolyte movements. Although considerable attention has been paid to the innervation of the external musculature and the control of motility, until the past few years comparatively little interest has been shown in the roles of submucous plexus on ion transport of epithelium. There are considerable evidence that submucous plexus is important for the regulation of intestinal secretion ; the submucous plexus regulates intestinal chloride secretion in mammalian species. Cholinergic secretomotor neurons have been implicated in the control of transport function on the basis of their proximity to the
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epithelium, release of acetylcholine by depolarizing agents, reduction in neurally-evoked secretion by muscarinic antagonists. The inability of cholinergic blockades to abolish neurally-evoked secretion suggests that non-cholinergic neurons, possibly peptidergic neurons, also influence epithelial function.
In this project, we have investigated the localization of neuropeptides and the action of various neuropeptides on ion transport in the guinea-pig distal colon.
In the guinea-pig colon, we found that the VIP-immunoreactive nerve fibers are penetrated into the mucosa and they terminate the beneath of the basolateral membrane of epithelial cells. VIP enhances the substance P- evoked chloride secretion at epithelial cell level. Substance P increases in [Ca^<2+>]i of isolated crypt cells but VIP fails to evoke increase in [Ca^<2+>]i crypt cells. Newly discovered neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP) produces concentration-dependent increase in chloride secretion. The response is primarily due to chloride secretion. Atropine significantly reduced the PACAP-evoked responses but did not abolish it. The results suggest that PACAP-evoked chloride secretion through cholinergic and non-cholinergic neural mechanism. TTX did not abolish the VIP-evoked response. The results suggest that VIP acts on both submucous neurons and epithelial itself. From this project, PACAP has different mechanism of chloride secretion to that of VIP. Whether VIP and PACAP receptors located on submucous neurons are the same or not are now under investigation. Less
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