| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
1. Coca-Cola topically applied to the mucosa for 10 min increased HCO_3^- secretion in both the stomach and the duodenum. The response in the duodenum was totally abolished by indomethacin and partially inhibited by acetazolamide, while the response in the stomach was inhibited by acetazolamide or indomethacin. Coca-Cola increased PGE_2 contents in both the stomach and the duodenum. These results suggest that Coca-Cola induces HCO_3^- secretion in both the stomach and duodenum, and the responses may be attributable to both the intracellular supply of HCO_3^-, by the aid of carbonic anhydrase, and endogenous PGs, probably related to the acidic pH of the solution.
2. PGE2 and NOR-3 increased HCO_3^- secretion in the mouse duodenum in vitro, and the response to PGE_2 was inhibited by both EP3 and EP4 antagonists, while that to NOR-3 was inhibited by methylene blue. Vinpocetine (PDE1 inhibitor) and cilostamide (PDE3 inhibitor) potentiated the response to PGE2. By contrast, the stimulatory action of NOR-3 was significantly potentiated by vinpocetine but not cilostamide. These results suggested that PDE1 and PDE3 are involved in the regulation of duodenal HCO_3^- secretion and that the response to PGE_2 is associated with both PDE1 and PDE3, while the response to NO is mainly modulated by PDE1.
3. Both NOR-3 and 8-brcGMP dose-dependently stimulated HCO_3^- secretion, and the response to NOR-3 was inhibited by methylene blue. Likewise, the secretion induced by NOR-3 or 8-br-cGMP was attenuated by ONO-8711 (EP1 antagonist) as well as indomethacin and potentiated by both vinpocetine and zaprinast. NOR-3 increased the mucosal PGE_2 content in a methylene blue-inhibitable manner. These results suggest that NO stimulates gastric HCO_3^- secretion mediated intracellularly by cGMP and modified by both PDE1 and PDE5, and this response is finally mediated by endogenous PGE_2 via the activation of EP1 receptors.
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