2010 Fiscal Year Final Research Report
Local regulatory mechanisms of gastroduodenal bicarbonate secretion :
| Project/Area Number |
20590264
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
TAKEUCH Koji Kyoto Pharmaceutical University, 薬学部, 教授 (00150798)
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| Co-Investigator(Renkei-kenkyūsha) |
KURIHARA Eitaro 京都薬科大学, 薬学部, 大学院生
SASAKI Yoko 京都薬科大学, 薬学部, 大学院生
KITA Kazutomo 京都薬科大学, 薬学部, 大学院生
ISE Fumitaka 京都薬科大学, 薬学部, 大学院生
OHASHI Yumi 京都薬科大学, 薬学部, 大学院生
TAKASUKA Hironori 京都薬科大学, 薬学部, 大学院生
TAKAHASHI Kento 京都薬科大学, 薬学部, 大学院生
KOYAMA Masafumi 京都薬科大学, 薬学部, 大学院生
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| Project Period (FY) |
2008 – 2010
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| Keywords | 十二指腸アルカリ分泌 / ガス状メディエーター / 硫化水素(H_2S) / 一酸化炭素(CO) / コリン作動薬(カルバコール) / ムスカリン受容体サブタイプ / M受容体ノックアウトマウト / D細胞 / ソマトスタチン |
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| Research Abstract |
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.
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