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Local regulatory mechanisms of gastroduodenal bicarbonate secretion :

胃十二指肠碳酸氢盐分泌的局部调节机制：

基本信息

批准号：
20590264
负责人：
TAKEUCH Koji
金额：
$ 3.08万
依托单位：
Kyoto Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

We demonstrated in the present study that 1) endogenous PGs and gas mediators such as NO, H_2S and CO, are involved in the local regulatory mechanism of the acid-induced duodenal HCO_3^- secretion, 2) NO and CO stimulate HCO_3^- secretion at least partly by increasing PG production, 3) the stimulatory action of H_2S is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurons, 4) PGE_2 stimulates HCO_3^- secretion via activation of EP3/EP4 receptors, and 5) both PDE1 and PDE3 are involved in the regulation of duodenal HCO_3^- secretion. In addition, we also found, using muscarinic (M) receptor knockout mice, that 6) the cholinergic stimulation of duodenal HCO_3^- secretion is mainly mediated by the activation of M1 and M3 receptors and modified by M4 receptors and that 7) the activation of M4 receptors inhibits the release of somatostatin from D cells and results in enhancement of the HCO_3^- response by removing the negative effect of somatostatin.

本研究证实：（1）内源性PG和气体介质NO、H_2S和CO参与了酸诱导的十二指肠HCO_3 ~-分泌的局部调节机制;（2）NO和CO至少部分通过增加PG的产生来刺激HCO_3 ~-分泌，3）H_2S的刺激作用部分由PG和NO以及辣椒素敏感的传入神经元介导。4）PGE_2通过激活EP_3/EP_4受体刺激HCO_3 ~-的分泌，PDE 1和PDE 3均参与十二指肠HCO_3 ~-分泌的调节。此外，我们还发现，使用毒蕈碱（M）受体敲除小鼠，胆碱能刺激十二指肠HCO_3^-分泌主要由M_1和M_3受体介导，并受M_4受体调节; M_4受体的激活抑制D细胞释放生长抑素，导致HCO_3^-分泌增加通过消除生长抑素的负面影响。