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Biomedical subjects

M Deleers

Publications and source records attributed to M Deleers.

At least 55 records · Page 3Linked to original sources
PubMed1983

Synergistic effect of hypoglycemic sulfonylureas and negative phospholipids on calcium transport: ionic and conformational aspects.

In a two-phase bulk system for the study of ionophoresis, the capacity of hypoglycemic sulfonylureas to translocate Ca2+ was enhanced in a synergistic manner by negatively charged phospholipids. High concentrations of Na+ or K+ had relatively little effect on sulfonylurea-mediated Ca2+ translocation. The acidity constant of hypoglycemic sulfonylureas ranged from 10(-5) to 10(-6). The conformation analysis of Ca2+ -gliquidone complexes with a 1:1 or 1:2 stoichiometry and of a hybrid complex between Ca2+ and both gliquidone and phosphatidylserine revealed configurations suitable for Ca2+ transport across a hydrophobic domain. These findings raise the possibility that the cationic response of the pancreatic B-cell to hypoglycemic sulfonylureas may be due primarily to an alteration of both Ca2+ and H+ transport.

Biological Transport↗
PubMed1983

Stoichiometry of calcium binding by hypoglycemic sulfonylureas.

In a two-phase bulk system for the study of Ca ionophoresis, certain hypoglycemic sulfonylureas, when added to the organic phase, were translocated into the aqueous medium. Nevertheless, the stoichiometry of Ca binding by these agents could be assessed by repeated mixing of the aqueous medium with organic phases. At saturation, the binding of Ca ranged from 0.5 to 1.0 mole/mole of sulfonylurea. A 1:1 molar ratio was observed with glibenclamide, and this was found to be compatible with the conformational analysis of the Ca-glibenclamide complex. There was a tight correlation between the stoichiometry of the Ca-sulfonylurea complex and the biological potency of each drug. This suggests that such a stoichiometry may be responsible, in part at least, for differences in the insulinotropic capacity of distinct hypoglycemic sulfonylureas.

Calcium↗
PubMed1983

Conformational analysis of mixed monolayers of phorbol ester and phospholipid.

A computational approach was used to study the conformation of mixed monolayers of amphiphilic molecules in order to characterize the assemblage of phospholipids around tumor-promoting and biologically inactive phorbol esters. The theoretical model was in fair agreement with both experimental data obtained in mixed monolayers of phorbol esters and dipalmitoylphosphatidylcholine spread at an air-water interface and the binding of phorbol esters to phospholipid bilayers. Thus, the present method may represent a useful tool to predict the orientation and molecular interaction of amphiphilic drugs at the membrane level.

Liposomes↗
PubMed1982

Interaction between phorbol esters and phospholipid in a monolayer model membrane.

The possible molecular interaction between phorbol esters and a phospholipid was examined in monolayer films at an air-water interface. The surface pressure isotherms indicated that, at close-to-physiological pressure, there existed a repulsive interaction between the phospholipid and biologically active phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12,13-didecanoate (PDD). There was a close parallelism between the relative biological potency of different phorbol esters, as tumour promoters, and the magnitude of their repulsive interaction with the phospholipid. These findings raise the possibility that a biophysical interference of phorbol esters with the phospholipid domain of biological membranes may represent an important determinant of their biological actions.

Binding Sites↗
PubMed1982

Influence of phorbol esters on ionophore-mediated calcium exchange-diffusion in liposomes.

The interference of phorbol esters upon the process of A23187-mediated calcium exchange diffusion was examined in multilamellar liposomes formed of different types of lipids and incubated at variable temperatures. Phorbol esters facilitated the process of calcium ionophoresis in liposomes formed of dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidyl-choline (DMPC) and incubated below transition temperature. The magnitude of this facilitating action was negatively correlated with the tumor-promoting capacity of the phorbol esters. The phorbol esters also facilitated calcium ionophoresis in liposomes formed of a mixture of DPPC and cholesterol, provided that the temperature exceeded 34 degrees C. The magnitude of the latter facilitating action was positively correlated with both the temperature and the tumor-promoting potency of the phorbol esters. Thus, the existence of a parallelism between the biological potency of phorbol esters and their biophysical effect in this artificial system tightly depended on such factors as the lipid composition of the liposomal matrix and the ambient temperature.

Anti-Bacterial Agents↗
PubMed1982

Influence of membrane viscosity on the lateral and transverse mobility of carboxylic ionophores.

The rate of 45Ca or 22Na exchange-diffusion in multilamellar liposomes formed of dipalmitoyl-phosphatidylcholine (DPPC) and cholesterol and containing the ionophore A23187 or Br-X537A was dramatically increased when the temperature and, hence, fluidity of the lipid bilayer were increased. In the case of 45Ca transport, i.e. when each Ca2+ ion binds to two molecules of ionophore, the relative increment in transport velocity in response to a given increase in temperature or fluidity was much more marked in the high range of temperature (30-40 degrees C) than in the low range of temperature (22-28 degrees C). In the case of 22Na transport, however, i.e. when each Na+ ion binds to only one ionophoretic molecule, the temperature-dependency of the transport process followed a single pattern throughout the entire range of temperature. In the latter case, the slope of the temperature-dependent line was the same as that seen for 45Ca transport by the same ionophore at high temperatures. A decrease in the ionophore content of the liposomes shifted to a higher temperature the transition point between the flat and steep lines characterizing the temperature dependency of 45Ca transport. It is concluded that the membrane viscosity affects both the lateral mobility of the ionophoretic molecules and the transverse mobility of the cation-ionophore complex.

Anti-Bacterial Agents↗
PubMed1982

Homologous and hybrid calcium complexes of A23187 and hypoglycemic sulfonylureas: nuclear magnetic resonance and conformational analysis.

Hypoglycemic sulfonylureas (e.g., gliclazide) are able to transport calcium across hydrophobic domains. Gliclazide and the ionophore A23187 act synergistically upon calcium transport. One calcium atom is complexed by either two molecules of sulfonylureas (or A23187) or one molecule each of sulfonylurea and A23187; the existence of such hybrid complexes has been documented by nuclear magnetic resonance. Conformation analysis of the calcium-gliclazide complex suggests close apposition of the toluyl groups in the gliclazide molecules.

Anti-Bacterial Agents↗
PubMed1982

Conformational analysis of the calcium--A23187 complex at a lipid--water interface.

A possible conformation of the complex formed by one calcium ion and two molecules of the ionophore A23187 at a simulated lipid--water interface was predicted by a variant method for conformational analysis. This method takes into account, in addition to the Van der Waals energy, electrostatic interaction, and torsional potential, the alteration of electrostatic forces attributable to changes in dielectric constant at the interface and the transfer energy for each part of the complex as it moves through the lipid-water interface. The most probable conformer was characterized by a two-fold axial symmetry that was maintained during transition to the hydrophobic bulk conformation. Minor changes in the interfacial structure were sufficient to achieve the configuration characteristic of the hydrophobic bulk phase.

Anti-Bacterial Agents↗
PubMed1981

Phorbol esters parallel effects on tumor promotion, insulin release and calcium ionophoresis.

The tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12,13-didecanoate (PDD) both stimulated insulin release from rat pancreatic islets and facilitated ionophore-mediated calcium transport in liposomes, the latter effect not resulting from a change in viscosity of the liposomial matrix. Phorbol and 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), which fail to cause tumor promotion, also failed to stimulate insulin release and ionophore-mediated calcium transport. An alteration of calcium transport may represent a fundamental event in both the early (insulin release) and late (tumor promotion) biological responses to phorbol esters.

Animals↗
PubMed1981

Formation of hybrid complexes between Ca and the ionophores bromolasalocid (Br-X537A) and A23187.

The ionophores A23187 and bromolasalocid (Br-X537A) acted synergistically in translocating Ca(2+) from an aqueous into an organic immiscible phase or in mediating Ca(2+) transport across the organic phase, the effects obtained in the simultaneous presence of both ionophores being greater than those expected from a summation of the individual effects of each ionophore. The nuclear magnetic resonance spectrum obtained when the complexation of Ca(2+) occurred in the presence of both ionophores differed strikingly from the individual spectra obtained with the A23187-Ca and Br-X537A-Ca complexes. These findings indicate that the two ionophores are able to form hybrid complexes with Ca(2+).

Journal Article↗
PubMed1981

Interaction of phorbol esters with lipid bilayers : thermotropic changes in fluorescence polarization, phase transition and calcium ionophoresis.

The influence of phorbol esters upon the thermotropic behaviour of multilamellar liposomes formed of dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) was investigated, as a model for possible interferences of the phorbol esters with the phospholipid domain of biological membranes. Both biologically active (TPA, 12-O-tetradecanoylphorbol-13-acetate, PDD, phorbol-12,13-didecanoate) and inactive (4 alpha-PDD, 4 alpha-phorbol-12,13-didecanoate) phorbol esters lowered the temperature required to cause a fall in fluorescence polarization of a fluorescent probe inserted in the lipid matrix of the DMPC or DPPC liposomes and facilitated the process of calcium exchange-diffusion in DPPC liposomes containing the ionophore A23187. Both of these effects could be due to a decrease in viscosity of the liposomal matrix. However, differential scanning calorimetry revealed that the thermotropic changes evoked by each of these phorbol esters were not identical. In most cases, the phorbol esters decreased both the main phase transition temperature and enthalpy of melting. However, when TPA was incorporated in DMPC liposomes, i.e. when a myristoyl chain was present in both the phorbol ester and phospholipid, no change in the enthalpy of melting could be detected, whereas the main phase transition temperature decreased in proportion to the TPA content of the liposomes. These findings emphasize the view that phorbol esters indeed interact with phospholipids and that the characteristics of such an interaction may tightly depend on the precise chemical structure of both the phorbol ester and phospholipid under consideration.

Calcimycin↗
PubMed1981

Inhibition of cationic liposomes of [3H]thymidine incorporation into DNA of L1210 cells.

The in vitro cytotoxicity of cationic liposomes for L1210 cells was studied by measuring in two hours incubation their effect on [3H] thymidine incorporation into DNA. Liposomes prepared from the mixtures dipalmitoylphosphatidylcholine-cholesterol-stearylamine, egg yolk phosphatidyl-choline-cholesterol-stearylamine and egg yolk phosphatidyl-choline-stearylamine inhibit [3H] thymidine incorporation into L1210 cells DNA. The degree of inhibition increases with incubation time and the concentration of liposomes in the incubations. Liposomes of similar compositions, but without stearylamine (neutral liposomes), did not affect [3H] thymidine incorporation. On the other hand, fluorescence microscopy of cell incubated with liposomes containing 10 mM 6-carboxy fluorescein showed only cationic liposomes adsorbed on the surface of L1210 cells. It is concluded that the inhibition of [3H] thymidine incorporation due to cationic liposomes is partly related to their adsorption on the cell plasma membrane.

Adsorption↗