1991 Fiscal Year Final Research Report Summary
Function, structure and regulation of two kinds of Cl^- channels involved in gastric acid secretion
| Project/Area Number |
02454115
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General physiology
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
TAKEGUCHI Noriaki Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00019126)
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Shinji Toyama Medical and Pharmaceutical University Faculty of Pharmaceutical Sciences,, 薬学部, 助手 (90167891)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Cl^- channel / proton pump / gastric acid secretion / H^+, K^+-ATPase |
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| Research Abstract |
Two different Cl- channels which are present in the basolateral and apical membranes of acid secreting cells are studied here. Usually, cell membrane potentials are determined by equilibrium potential to K+ : that is, K+ conductance determines the potential. But in the rabbit parietal cell, the membrane potential was found to be determined by Cl- channel in the basolateral membrane. The single Cl- channel conductance was found to be only 0.3 pS from an experiment of patch clamp-ensemble noise analysis. The Cl- channel was activated by arachidonic acid (AA) and prostaglandin E2 (PG), and inhibited by GTP S. In other types of cells, AA and PG are known to inhibit Cl- channel and GTP S activates the channel, which is in contrary to what found for the present gastric Cl- channel. Regulation of the cell membrane potential via the Cl- Channd engages in cytoprotection against strong gastric acid and stress.
Isolation of parietal cells results in formation of occluded canaliculus and the apical membrane is not able to be reached from the cell surface by a micropipette. We found that oxyntic cells isolated from red belly newt expose both the basolateral and apical membranes to the bath medium from an experiment in which acid-activated proton pump inhibitor, methoxy E3810, was poured on the surface of the isolated cell, the S-S cross-linked inhibitor was irradiated with ultraviolet light, and the increase in the fluorescence was measured. The distribution of the pump was obtained from the image fluorescence analysis of single cells. Using the oxyntic cells we succeeded to detect the apical Cl- channel although more detailed study is necessary to characterize the apical Cl- channel.
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