1994 Fiscal Year Final Research Report Summary
Physiological study of Cl^- channels associated with gastric proton pump and liver multidrug efflux pump
| Project/Area Number |
05454139
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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 & Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00019126)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Gastric proton pump / multidrug efflux pump / Cl^- channel |
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| Research Abstract |
Gastric proton pump is the terminal target of the stimulus-secretion coupling in the acid secretory mechanism. In 1987, we found that Cl^- channel was the part of the function of this proton pump ; that is, two functions of the Cl^- channel and the proton pump are coexisted in the same molecule. In 1992, Cambridge and Oxford researchers found a similar finding with the multidrug efflux pump.
In the first year of this grant, we established the model system in which the function of multidrug efflux pump was visualized and the side effect of cyclosporin in liver transplantation was found to be due to inhibition of the multidrug efflux pump by cyclosporin (Transplantation, 1993). The inhibition of the efflux pump was not found with FK506 at the clinical dose. The conformation of gastric proton pump was differently affected by omeprazole and E3810 which are irreversible inhibitors (J.Biol.Chem., 1993). We also found a new type of Cl^- channel in the gastric acid secreting cell (J.Physiol., 1993).
In the second year, we studied the intracellular transport of the pump bound by the inhibitors (Biochem.Phannacol., 1994). The C-terminal topology of this pump in the membrane was studied by raising a monoclonal antibody (Biochem.J., 1994). The molecular structure of gastric proton pump is slightly different from that of the colonic proton pump. We succeeded to raise two monoclonal antibodies ; one binds only to the gastric pump and the other binds to both pumps (J.Biochem., 1994). The intracellular regulatory mechanism of the cytoprotective Cl^- channel was also studied (J.Biol.Chem., 1994). We also prepared cDNAs which encode alpha and beta subunits of gastric proton pump.
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