Contribution of hydrophobicity of nonionic detergents to membrane lipid fluidity and disopyramide uptake by rat intestinal brush-border membrane vesicles.
The contribution of hydrophobicity of different types of detergents to disopyramide uptake by rat small intestinal brush-border membrane vesicles was studied in relation to their membrane lipid fluidity and the physicochemical parameters of the detergents, i.e., hydrophile-lipophile balance (HLB). Span-, Tween-type detergents or glycerol esters at non-solubilizing concentrations (0.01-0.05% (w/v)) decreased the extent of maximum uptake of the drug in the presence of outward H(+)-gradient, but not in the absence of the gradient. The fluorescence anisotropy of the vesicles using diphenylhexatriene (DPH), as reflected by its incorporation into the membrane inner lipid layer, decreased with the addition of all detergents used. In contrast, that of the vesicles using trimethylammoniumphenyl phenylhexatriene (TMA-DPH), which reflected its incorporation into the membrane outer lipid layer, increased depending on the concentration of Tween-type detergents except for Tween 81 and Tween 85, glycerol esters (MO-500, MO-750, ML-500 and ML-750); it decreased with the addition of Span-type detergents, Tween 81 and glycerol ester (MO-310). Therefore, the membrane lipid fluidity change of the outer leaflet, rather than the inner lipophilic domain, of the membrane vesicles caused by the detergents was found to be dependent on the hydrophobicity, but not on the type of detergent. This seems to correlate with the inhibitory effects on the facilitated uptake of the drug by the membrane vesicles.
Koga
K
K
Division of Pharmaceutical Information, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Murakami
M
M
Kawashima
S
S
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology*; D004206:Disopyramide / Q000378:metabolism*; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D003902:Detergents; D005456:Fluorescent Dyes; D008563:Membrane Lipids; D004206:Disopyramide