| Project/Area Number |
05671818
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
MUTO Norio Osaka University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30112642)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Keiichi Osaka University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90068247)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Ascorbic acid / Ascorbate-binding protein / Membrane transport / Toxicity evaluation |
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| Research Abstract |
(1) In order to clarify the molecular aspect of ascorbate transport system, membraneous ascorbatebinding activity was studied by using CHAPS-solubilized preparation of rat kidney membranes. This binding activity was effectively inhibited by the addition of ascorbate and a high dose of dehydroascorbate, whereas glucose and glucose-transport inhibitors showed no inhibition.Moreover, this preparation was found to bind the reduced form of ascorbate, strongly supporting the presence of an ascorbate-specific binding protein which is considered to be a member of its transport system on the plasma membranes. (2) This binding protein was separated by gel filtration with a good retention of activity and its molecular weight was estimated to be about 100kDa. However, further purification was not achieved by any chromatography until now, resulting in remarkable decrease of activity. For its purification, it is necessary to establish the conditions to reconstitute the binding complex. (3) In this project we have found for the first time that gastric ascorbate secretion is mediated via cholinergic receptor and this mechanism is responsible for physiological importance of ascorbate in the stomach. In addition, the absorption efficiency of ascorbate in the small intestine was found to be influenced by nicotine. These results suggest that environmental pollutants dynamically affect the transport system of ascorbate in the gut. We need further investigation to establish ascorbate-specific uptake system of cell line for evaluation of toxicity by pollutants.
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