Back to Search
Start Over
Presence of anionic phospholipids rules the membrane localization of phenothiazine type multidrug resistance modulator.
- Source :
-
Biophysical chemistry [Biophys Chem] 2004 Jun 01; Vol. 109 (3), pp. 399-412. - Publication Year :
- 2004
-
Abstract
- Substances able to modulate multidrug resistance (MDR), including antipsychotic phenothiazine derivatives, are mainly cationic amphiphiles. The molecular mechanism of their action can involve interactions with transporter proteins as well as with membrane lipids. The interactions between anionic phospholipids and MDR modulators can be crucial for their action. In present work we study interactions of 2-trifluoromethyl-10-(4-[methanesulfonylamid]buthyl)-phenothiazine (FPhMS) with neutral (PC) and anionic lipids (PG and PS). Using microcalorimetry, steady-state and time-resolved fluorescence spectroscopy we show that FPhMS interacts with all lipids studied and drug location in membrane depends on lipid type. The electrostatic attraction between drug and lipid headgroups presumably keeps phenothiazine derivative molecules closer to surface of negatively charged membranes with respect to neutral ones. FPhMS effects on bilayer properties are not proportional to phosphatidylserine content in lipid mixtures. Behavior of equimolar PC:PS mixtures is similar to pure PS bilayers, while 2:1 or 1:2 (mole:mole) PC:PS mixtures resemble pure PC ones.<br /> (Copyright 2003 Elsevier B.V)
- Subjects :
- Anions chemistry
Calorimetry, Differential Scanning
Cations chemistry
Cell Membrane Permeability
Hydrophobic and Hydrophilic Interactions
Phosphatidylserines chemistry
Phosphatidylserines metabolism
Spectrometry, Fluorescence
Temperature
Drug Resistance, Multiple
Lipid Bilayers chemistry
Phenothiazines chemistry
Phospholipids chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0301-4622
- Volume :
- 109
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biophysical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15110937
- Full Text :
- https://doi.org/10.1016/j.bpc.2003.11.004