Regulation of water and electrolyte transport in the gut

肠道内水和电解质运输的调节

• 批准号: 04044178
• 负责人: KUWAHARA Atsukazu
• 金额: $ 7.42万
• 依托单位: National Institute for Physiological Sciences, Okazaki National Research Institutes
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04044178/
• 关键词: enteric nervous system; ion transport; neuropeptide; chloride; secretion; colon; gastrointestinal tract; receptor; guinea-pig; 壁内神経

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 … More 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

肠道是一个复杂的器官，由于其结构的异质性，肠道由肌肉，神经丛和粘膜组成。肠道的肌肉和粘膜中发现了广泛的神经纤维网络。这些纤维大部分来自肌间神经丛或粘膜下神经丛中的神经节细胞。这些神经丛调节胃肠功能，包括运动、水和电解质运动。虽然相当多的注意力已经支付给外部肌肉组织的神经支配和运动的控制，直到过去几年比较少的兴趣已被显示在粘膜下神经丛上皮细胞的离子转运的作用。有相当多的证据表明，粘膜下神经丛是重要的肠道分泌的调节;粘膜下神经丛调节肠道氯化物分泌在哺乳动物物种。胆碱能分泌运动神经元与转运功能的控制有关，这是基于它们与神经元的邻近性。 ...更多信息 上皮，去极化剂释放乙酰胆碱，毒蕈碱拮抗剂减少神经诱发分泌。胆碱能阻断不能消除神经诱发的分泌提示非胆碱能神经元，可能是肽能神经元，也影响上皮功能。在本项目中，我们研究了豚鼠远端结肠中神经肽的定位和各种神经肽对离子转运的作用。在豚鼠结肠中，我们发现VIP免疫反应阳性神经纤维穿入粘膜，它们终止于上皮细胞的基底外侧膜之下。VIP在上皮细胞水平增强P物质诱导的氯分泌. P物质使离体腺细胞[Ca^<2+>]i增加，VIP则不能引起[Ca^<2+>]i增加。新发现的神经肽垂体腺苷酸环化酶激活肽（PACAP）产生浓度依赖性的氯分泌增加。反应主要是由于氯化物分泌。结果表明，PACAP通过胆碱能和非胆碱能神经机制诱发氯化物分泌。TTX不能消除VIP诱发的反应。提示VIP不仅作用于粘膜下神经元，而且作用于上皮细胞本身。由此可见，PACAP的泌氯机制与VIP不同。粘膜下神经元上的VIP和PACAP受体是否相同还有待进一步研究。少

项目成果

Nagahama,M.,Tsutsui,Y.,Kuwahara,A.and Akagawa,K.: "Immunohistochemical demonstration of neuron specific antigen,HPC-1 in the enteric nervous system of the guinea-pig colon." Neuroscience Letters. 160. 37-40 (1993)

Nagahama, M.、Tsutsui, Y.、Kuwahara, A. 和 Akakawa, K.：“豚鼠结肠肠神经系统中神经元特异性抗原 HPC-1 的免疫组织化学演示。”

Yanaihara,N., Mochizuki,T., Ohshima,K., Takatuka,N., Iguchi,K., Hoshino,M., Kuwahara,A. and Yanaihara,C.: "Galanin-A novel multifunctional peptide : The further development." Gut Hormone. 12. 1-14 (1993)

柳原，N.，望月，T.，大岛，K.，高冢，N.，井口，K.，星野，M.，桑原，A.

Yanaihara,C. Kuwahara,A., Suzuki,M., Hoshino,M., Zheng,Li L.-Q., Kashimura,K., Takeda,Y., Iguchi,K., Mochizuki,T. and Yanaihara N.: "Novel CCK analogues for studying CCK-B receptor" New York Academy of Science (in press).

柳原，C.

A.Kuwahara,Y.Kuwahara,T.Suzuki,Y.Sakai,T.Mochizuki and N.Yanaihara: "PACAP evokes chloride secretion in guinea-pig distal colon." Biomedical Research″Vasoactive Intestinal Peptide and Related Peptides″. 13(Supp1.2). 343-346 (1992)

A. Kuwahara、Y. Kuwahara、T. Suzuki、Y. Sakai、T. Mochizuki 和 N. Yanaihara：“PACAP 引起豚鼠远端结肠中的氯离子分泌。”生物医学研究“血管活性肠肽和相关肽”。补编1.2）。343-346（1992）。

A.Kuwahara,K.Kimura,T.Ozaki T.Suzuki and N.Yanaihara: "Galanin as an inhibitory neurotransmitter in regulation of muscle activities in the gastro-intestinal tract." Gastrointestinal Function:Regulation and Disturbances.Excerpta Medica International Congre

A.Kuwahara、K.Kimura、T.Ozaki T.Suzuki 和 N.Yanaihara：“甘丙肽作为抑制性神经递质，调节胃肠道肌肉活动。”