| Project/Area Number |
05671795
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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 |
Physical pharmacy
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| Research Institution | Niigata College of Pharmacy |
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Principal Investigator |
KITAGAWA Shuji Ph.D.Niigata College of Pharmacy, Department of Pharmaceutics, Professor, 薬学部, 教授 (00108911)
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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 |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Transdermal drug penetration / Small intestinal brush border membrane / Membrane fluidity / Alcohol / Fatty acid / Mg^<2+>-ATPase / Liposome / Fluorescence probe / アルカリ性ホスファターゼ |
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| Research Abstract |
Mechanisms of modification of biological membrane functions by amphiphilic compounds such as alcohols and fatty acids were studied for small intestinal brush border membrane and skin. The effects of seven n-alkyl alcohols (from n-butyl to n-undecyl alcohol) , isoamyl alcohol and benzyl alcohol on activity of membrane enzyme Mg^<2+>-ATPase of the rabbit small intestinal brush border membrane were examined and their relationships with changes in fluidity of the membrane lipid bilayr were investigated. The extents of decreases in activeties of the membrane enzyme Mg^<2+>-ATPase by all the alcohols clearly corresponded with their extents of decreases in fluorescence anisotropy of diphenylhexatriene (DPH) . These results suggest the possibility that inhibition of this enzyme by the alcohols can be explained by perturbation of the lipid bilayr of the brush border membrane.
Phase transition of the lipid bilayr of liposomes of stratum corneum lipids was also examined at different pH values by monitoring the fluorescence anisotropy of DPH.The phase transition temperature decreased about 15 deg. C with decrease of the pH from 6.2 to 4.0. The decrease depended on the content of palmitic acid en liposomes and corresponded with the protonation of the anionic form of fatty acid. Stumulation of in vitro transdermal penetration of phenol at acidic pH was observed which was consistent with the results on liposomes. A pH-dependent decrease of the phase transition temperature of liposomes was also observed on replacement of palmitic acid by other fatty acids. In the presence of lauric acid at pH 4.0, the fluorescence anisotropy of DPH also decreased at physiological temperatures, this effect being similar to those of long-chain cis-unsaturated fatty acids.
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