The asymmetric distribution of chlorpromazine and its quaternary analogue over the erythrocyte membrane (original) (raw)
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Fluorescence studies of membrane interactions of chlorpromazine and chlorimipramine
Biochemical Pharmacology, 1977
The location of chlorpromazine and chlorimipramine, when these drugs are bound by the erythrocyte membrane, is discussed. The binding of these drugs to ghosts, to liposomes of erythrocyte ghost lipid and to isolated ghost proteins suggest that both the lipid and the protein phase are binding domains. The average distance between drug and membrane tryptophan was determined by fluorescence spectroscopy. These results and experiments with the fluorescent probe 1-anilinonaphtalene-8-sulfonate (ANS) confirmed the indicated location.
Binding of two spin-labelled derivatives of chlorpromazine to human erythrocytes
Biochemical Journal, 1989
The binding to human intact erythrocytes of two different spin-labelled derivatives of chlorpromazine has been studied. The influence of the positively charged side chain of the drug has been the focus of our attention. The positively charged amphiphilic compound (spin derivative I) is water-soluble up to 80 microM at pH values below 5.9. The apolar analogue (spin derivative II) aggregates in aqueous buffer from the lowest concentration tested. Both spin derivatives undergo a slow reduction inside the erythrocyte. The reduced nitroxides are readily reoxidized by adding a low, non-quenching, concentration of potassium ferricyanide to the intact erythrocytes. The fractions of spin label I and II bound to the erythrocyte membrane or to the erythrocyte-extracted lipids remain constant as a function of the temperature (3-42 degrees C) and as a function of the concentration of the spin label up to 150 microM. E.s.r. spectra of both spin labels show a two-component lineshape when they are ...
Interaction of chlorpromazine with phospholipid membranes
European Biophysics Journal, 1995
Chlorpromazine penetration into the lipid core of the membrane was demonstrated through measurements on lipid monolayers (surface pressure and surface potential). The surface pressure measurements allow us to calculate the intrinsic binding constant (partition coefficient) for the lipid-Chlorpromazine interaction. This latter value is in correct agreement with the obtained results by electrophoretic mobilities measurements on liposomes.
The influence of chlorpromazine on the potential-induced shape change of human erythrocyte
Bioscience Reports, 1991
The effect of chlorpromazine (CPZ) on the shape of human erythrocytes with different values of transmembrane potential (TMP) was investigated. The shape of red blood cells with negative values of the TMP remained unchanged after the formation of stomatocytes by chlorpromazine, while cells with positive TMP showed a characteristic time course of shape change during the incubation with CPZ. Experiments with vanadate show that this might be due to a difference in the activity of the phospholipid-translocase at different values of TMP.
Influence of chlorpromazine and its derivatives on the dynami of lipid membranes
2012
Perturbation effect of the tranquilizers chlorpromazine, chlorprothixene, levopromazine, thioridazine, and perfenazine on lipid membranes was studied using the electron spin resonance spectroscopy of stearic acid spin labeled at the position 16. The order parameter S of the spin probe in the lipid membranes depending either on the membrane order and/or dynamics of the hydrophobic membrane part was used to estimate the perturbation effect of the drugs. Chlorpromazine increased the order parameter S of the probe in lecithin liposomes, and decreased the parameter S in the liposomes prepared from the rat brain total lipid/lecithin mixtures. The disordering effect of chlorpromazine increased with the increase of the total lipid/lecithin mass ratio in the liposomes. The tranquilizers showed different propensities to decrease the S parameter of the probe in the liposomes prepared from the total lipids. The propensities with the individual compounds increase in the order: perfenazine, levop...
Oxidative Medicine and Cellular Longevity
The purpose of this paper is to focus on the short-term effects of chlorpromazine on erythrocytes because it is reported that the drug, unstable in plasma but more stable in erythrocytes, interacts with erythrocyte membranes, membrane lipids, and hemoglobin. There is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore the influence of long-term treatment. We think that evaluating the short-term effects of the drug may help to clarify the sequence of chlorpromazine molecular targets from which some long-term effects derive. Our results indicate that although the drug is primarily intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of caspase 3, and, markedly, influences the ATP and reduced glutathione levels...
Phenylhydrazine-induced changes in erythrocyte membrane surface lipid packing
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1986
Phenylhydrazine-induced oxidative damage in red cells results in increased binding of merocyanine 540, a fluorescence probe sensitive to changes in lipid packing. Fluorescence polarization studies with diphenylhexatriene did not reveal major changes in order parameters both in intact red cells and lysates treated with phenylhydrazine. These fluorescence studies indicate that major changes are observed in membrane iipids. Analytical studies of membrane phospholipids revealed a significant decrease in phosphatidylethanolamine. The results of the fluorescence and lipid studies, taken in association with our previously reported findings on spectrin and other cytoskeletal protein degradation in red cells exposed to phenylhydrazine, suggests that degradation of cytoskeleton membrane proteins is also responsible for changes in the lipid bilayer surface of the red cell membrane.
Biochimica Et Biophysica Acta - Biomembranes, 1986
Partition coefficients, kp, of chlorpromazine between the aqueous phase and lipid bilayer vesicles were determined as function of drug concentration, lipid chain length, cholesterol content and temperature encompassing the range of the lipid phase transition. Radioactivity and absorption measurements were performed to determine the kp values. Up to a concentration of 3. l0-s M, the partition coefficient is independent of chlorpromazine concentration, whereas it decreases drastically at higher chlorpromazine concentrations, at which membrane lysis is observed. Membrane structure is not disturbed at less than 3.10-s M chlorpromazine, as was concluded from electron paramagnetic resonance studies measuring TEMPO partitioning and order degree. However, the lipid phase-transition temperature decreases and is broadened at higher chlorpromazine concentrations. From fluorescence measurements, we conclude the formation of chlorpromazine micelles at concentrations higher than 5-l0-5 M in chlorpromazine in the absence of lipids and the formation of mixed micelles in the presence of lipids. The effect of lipid chain length on kp values was investigated. The partition coefficient decreases from 8100 in dilauroyi-to 3400 in dipalmitoylphosphatidyicholine vesicles, both at 50°C, that is, above their corresponding phase-transition temperature t t. At t < t t the kp values are strongly reduced, by at least a factor of 10, depending on lipid chain length and membrane composition. It is possible to establish a lipid phase-transition curve from the temperature-dependent measurements of the kp values. Cholesterol within the lipid membrane strongly decreases kp. At 20 mol% cholesterol in dipalmitoylphosphatidylcholine membranes, the partition coefficient is reduced from 3400 to 2300. This value is well comparable to the kp value obtained in erythrocyte ghosts. In contradiction to earlier experiments by Conrad and Singer (Biochemistry 20 (1981) 808-818), this value in a biological membrane could be obtained by the hygroscopic desorption as well as the centrifugation method. From our experiments we are justified in further considering artificial bilayer membranes as models for biological membranes.
Biochemistry, 1986
The binding of [*03Hg] p(ch1oromercuri)benzenesulfonate to the membrane proteins of human erythrocytes and erythrocyte ghosts was examined under conditions where binding to the bulk of membrane sulfhydryl groups was blocked by N-ethylmaleimide. Binding was essentially complete within 90 min when approximately 40 nmol was bound per milligram of membrane protein. This binding was correlated with the inhibition of water transport measured by an N M R technique. Maximal inhibition was observed with the binding of approximately 10 nmol of p-(chloromercuri)benzenesulfonate/mg of membrane protein. Under these conditions, both band 3 and band 4.5 bound 1 mol of inhibitor/mol of protein. In contrast to previous experiments, these results indicate that band 4.5 proteins as well as band 3 have to be considered as playing a role in water transport.