Mechanism for the Enhancement of Intestinal Paracellular and Transcellular Permeability by Absorption Promoters
| Project/Area Number |
60571094
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tokyo College of Pharmacy |
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Principal Investigator |
MASAHIRO Hayashi Tokyo College of Pharmacy, 薬学部, 助教授 (20012669)
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| Co-Investigator(Kenkyū-buntansha) |
TOSHIHARU Horie Tokyo College of Pharmacy, 薬学部, 講師 (90120154)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | absorption promoter / paracellular route / transcellular route / water absorption / pore radius / fluorescence polarization / 蛍光偏光解消法 / 膜流動性 |
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| Research Abstract |
The effects of absorption promoters on two possible transport pathways, paracellular and transcellular routes, were investigated. For the paracellular routes, the increase in water absorption, which was suppressed by a Na-K pump inhibitor such as ouabain and the enlargement in pore size (radius) of water filled channel were found by in situ loop and in vitro everted sac techniques, respectively. Such paracellular promoters were EDTA, taurocholic acid (TC), medium chain fatty acid, and mixed micelles of oleic aced and TC. Especially, capric acid (C10), lauric acid (C12) and mixed micelles were effective even at low concentrations. Antipyrine (AP), phenol red and cefmetazole (CMZ) were absorbed through the paracellular routes. Enlarged pore sizes correlated with the degree of promoting effects and enabled water soluble and high molecular weight compound, inulin, to permeate through them. Simultaneous luminal and vascular perfusion method showed that the increase in water absorption related to that in absorption site blood flow. For the change in transcellular permeability, membrane-perturbing actions of the above promoters were studied by fluorescence polarization technique. The brush border membrane (BBM) vesicles where its protein and lipid portions were labelled with fluorescent probes were used. The release of 6-carboxyfluorescein (CF) enclosed into BBM vesicles was also examined. Salicylic acid and C8 were found to interact mainly with membrane protein but C10 and C12, with both protein and lipid, causing the membrane perturbation. CF release was larger for C10 and C12 than for salicylic acid and C8. The results indicated that the degree of perturbation corresponded to that of membrane permeability of CF and also absorption promotion in situ. Consequently, it was shown that most promoters are paracellular ones and also can increase the permeability in transcellular routes through the membrane perturbation.
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Report
(1 results)
Research Products
(11 results)
