| Project/Area Number |
02807200
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
INUI Ken-ichi Tokyo Medical and Dental University, School of Medicine, Department of Hospital pharmacy, Professor, 医学部, 教授 (70034030)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Hideyuki Tokyo Medical and Dental University, School of Medicine, Department of Hospital, 医学部, 助手 (40225727)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Intestinal Epithelial Cell / Renal Epithelial Cell / Cultured Epithelial Cell / Transporter / Transcellular Transport / Organic Cation / Dipeptide / Proton-Coupled Transport / 刷子縁膜 / 吸収・分泌 |
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| Research Abstract |
We have studied the cellular and molecular mechanisms of the drug transporters such as H^+/organic cation antiporter (secretion) in the renal brush-border membranes and H^+/dipeptide cotransporter (absorption) in the intestinal brush-border membranes.
1) Substrate Specificity of the H^+/Organic Cation Antiporter and H^+/Dipeptide Cotransporter : Anticancer agent bestatin, a dipeptide containing an unusual amino acid, was transported via the H^+/dipeptide cotransporter in the intestinal brushborder membranes, and via the H^+/organic cation antiporter and the H^+/dipeptide cotransporter in the renal brush-border membranes.
2) Transcellular Transport of Organic Cation across Monolayers of Kidney Epithelial Cell Line LLC-PK_1 : Tetraethylammonium (TEA) was taken up progressively by the cell monolayers from the basolateral side, and was transported unidirectionally to the apical side. The basolateral-to-apical transport of TEA was stimulated by lowering pH of the apical side. The TEA efflux from the cell monolayers to the apical side caused a decrease in the intracellular pH.
3)Transcellular Transport -of Oral Cephalosporins and Bestatin by Monolayers of Human Intestinal Epithelial Cell Line Caco-2 : Oral cephalosporins accumulated in the Caco-2 cell monolayers via the H^+/dipeptide cotransporter localized in the apical membranes and that a specific transport system was involved in the efflux of these antibiotics across the basolateral membranes.
4)Expression of Dipeptide Transporters in Xenopus Oocytes : The expression of H^+-dependent dipeptide transporters was observed in Xenopus laevis oocytes injected with poly (A)^+mRNA from Caco-2 cells.
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