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K Ondrias

Publications and source records attributed to K Ondrias.

66 records · Page 4Linked to original sources
PubMed1988

Histamine liberation and membrane fluidisation of mast cells exposed to the beta-adrenoceptor blocking drug propranolol.

Propranolol liberates histamine from isolated mast cells and decreases the uptake of extracellular histamine in a dose-dependent way. Histamine liberation due to propranolol is accompanied by calcium displacement from intracellular storage sites. The significant increase in membrane fluidity due to propranolol is temperature dependent. The perturbation of membranes is most probably the explanation of propranolol's interaction with isolated rat mast cells which results in altered histamine transportation.

Animals↗
PubMed1987

Spin label study of the perturbation effect of the local anaesthetics tetracaine and dibucaine on synaptosomes at pharmacological concentrations.

The method of electron spin resonance spectroscopy of spin probes was used to determine the lowest concentrations of the local anaesthetics dibucaine and tetracaine exerting perturbations on synaptosome membranes. The perturbation depends on the temperature and the membrane depth, as well as on the concentration and the structure of the anaesthetics. Using spin labelled stearic acid at the 5th carbon position a negligible effect of the anaesthetics on the order parameter was found in the membrane both at 1 degree and 22 degrees, within the buffer concentration 0.01-10 mmol/l, but at 37 degrees and concentrations higher than 0.1 mmol/l the disordering effect was significant and of comparable efficiency for dibucaine and tetracaine. Employing stearic acid labelled at the 16th carbon position, disordering of the hydrocarbon core of the membrane caused by tetracaine or dibucaine was detected at 1 degree and 22 degrees, as well as at 37 degrees. The disordering effect occurred at buffer concentrations higher than 0.01 mmol/l for dibucaine, and higher than 0.1 mmol/l for tetracaine. At equal anaesthetic membrane concentrations and at the 16th carbon membrane depth, dibucaine was approximately twice as effective as tetracaine in perturbing synaptosomes. Tetracaine induced nonlamellar phases in the rat brain lipid membrane as detected by 31P NMR spectroscopy. The dynamic and structural perturbation effects of the local anaesthetics was found in that concentration range at which the anaesthetics influence various activities of biological membranes.

Anesthetics, Local↗
PubMed1987

Comparison of the effect of eleven beta-adrenoceptor blocking drugs in perturbing lipid membrane: an ESR spectroscopy study.

The perturbation effect of the beta-adrenoceptor blocking drugs atenolol, propranolol, practolol, oxprenolol, doberol, pronethanol, metipranolol, alprenolol, Kö-1124, pindolol, and exaprolol on rat brain lipid membrane was investigated by ESR spectroscopy using the spin probe method. Using stearic acids spin labeled at the 5th, 12th, and 16th positions, it was found that lipophilic drugs disorder the membrane and their effect is about 5-10 times higher at the 16th carbon membrane depth than at the 5th depth. Exaprolol induced nonlamellar phases in the bovine brain lipid membrane as detected by 31P NMR spectroscopy. The relative potencies of the drugs at 10 mmol/liter concentration to disorder the lipid membrane at the 16th carbon depth were in the order: exaprolol greater than alprenolol approximately equal to propranolol greater than metipranolol approximately equal to doberol greater than control sample greater than pindolol approximately equal to practolol approximately equal to atenolol. This order qualitatively corresponds with some of their nonspecific biological membrane activities but is not related to their beta-adrenoceptor blocking potencies. The inequality of the membrane perturbation propensities of the drugs indicates that they perturb the lipid membrane in a structure-dependent manner, i.e., that each induces a specific rather than a nonspecific membrane perturbation.

Adrenergic beta-Antagonists↗
PubMed1987

pH-dependent effects of local anaesthetics in perturbing lipid membranes.

The effects of local anaesthetics lidocaine, benzocaine, carbisocaine and carbisocaine derivatives, KaQ-7 and Ka-O, in perturbing bovine brain lipid membranes or egg lecithin membranes were compared at pH 6.0; 7.0; and 8.0. The electron spin resonance method with stearic acid labeled at carbon position 16 as the spin probe was employed. The perturbation effects of lidocaine and Ka-O were found to increase with increasing pH of the sample, whereas the effect of carbisocaine decreased with increasing pH. The perturbation effects of benzocaine and KaQ-7 were independent of pH. The pH-dependent perturbation effects of the local anaesthetics tested on lipid membrane fairly corresponded with their pH-dependent potency to block nerve action potentials.

Anesthetics, Local↗
PubMed1986

Modulation of rat testicular LH/hCG receptors by membrane lipid fluidity.

The specific binding of [125I]hCG to rat testicular membrane preparations was investigated as a function of membrane fluidity changed by lipids. Membrane fluidity was measured either by fluorescence depolarization of diphenylhexatriene or ESR spectra of I(1,14), I(12,3) and CAT 16 incorporated into the membrane. Incubation of membrane with cholesteryl-hemisuccinate increased both the rigidity of membrane lipids and the specific binding of [125I]hCG. A similar rigidifying action of saturated fatty acids was, however, not accompanied by increased accessibility of LH/hCG receptors. Treatment of testicular membranes with unsaturated fatty acids enhanced membrane fluidity but specific binding of the gonadotropin disappeared. In spite of the increase of LH/hCG receptors in cell membranes treated with cholesteryl-hemisuccinate, Leydig cells showed decreased sensitivity to cAMP response to LH stimulation. The results indicate that newly exposed LH/hCG receptors are not coupled with the adenylate cyclase system.

Animals↗
PubMed1986

Perturbation of lipid membranes by local anaesthetic carbisocaine.

Local anaesthetic carbisocaine decreased the electrical conductivity of gramicidin channels in planar lipid membrane made from bovine brain total lipids in n-hexane at the concentration (1.6 +/- 1.3) X 10(-5) mol/l, which is similar to that found to block propagation of action potential on the sciatic nerve. To study the mechanism of this effect the authors investigated the disordering effect of carbisocaine on rat total lipid membranes at the 5th, 12th and the 16th carbon membrane depths, using ESR spectroscopy of spin-labelled stearic acids. Carbisocaine disorders the membrane and the effect increases towards the methyl terminal of the lipid acyl chains. It is suggested that carbisocaine-induced perturbation of the membrane may have a secondary influence on the conductivity of gramicidin channels in the membrane.

Anesthetics, Local↗
PubMed1985

The interaction of beta-adrenoceptor blocking drugs with platelet aggregation, calcium displacement and fluidization of the membrane.

beta-Adrenoceptor blocking drugs interfere with adenosine diphosphate-stimulated platelet aggregation. Alprenolol, exaprolol, Kö 1124 and propranolol inhibited the aggregation, metipranolol decreased the extent and rate of aggregation significantly. Atenolol potentiated the aggregation measured by amplitude significantly. The interaction of beta-adrenoceptor blocking drugs with aggregation correlated with the displacement of calcium ions from binding sites in isolated platelets and the fluidization of the whole platelets and isolated platelet membrane as measured with electron spin resonance of the spin probe. The most potent were highly liposoluble drugs alprenolol, exaprolol, metipranolol and propranolol which increased the calcium displacement and membrane fluidity, the least active was atenolol decreasing these phenomena. The inhibition by beta-adrenoceptor blocking drugs of stimulated platelet aggregation is rather a result of unspecific than specific receptor interaction.

Adenosine Diphosphate↗
PubMed1984

Perturbation effect of local anaesthetics on synaptosomes: variation with depth of the spin label probe.

Stearic acids labeled with a doxyl group at the 5th, 12th and 16th carbon positions were used as the spin probes for an investigation of the perturbation effects of two local anaesthetics (the 2-piperidinoethylester of phenyl carbamic acid and the piperidinoethylester of 2-heptyloxyphenylcarbamic acid) on rat brain synaptosomes. For a quantitation of the perturbation effects we have studied the order parameter S of the spin probe, incorporated in the membrane, calculated from the ESR spectra as a function of temperature and concentration of local anaesthetics. The local anaesthetics had a different disordering efficiency at different depths of the membrane. It follows from our results that the perturbing effects of the anaesthetics increase relative to the depth of the membrane, and the extent of perturbation correlates with local anaesthetic activity.

Anesthetics, Local↗
PubMed1984

Effects of tertiary amine local anaesthetics on the phase behaviour of the dipalmitoylphosphatidylcholine model membrane. Electron spin resonance tetrametylpiperidinyloxyl partition study.

Using the electron spin resonance technique of the spin probe (TEMPO) is shown that local anaesthetics lidocaine, tetracaine, dibucaine, heptacaine and carbizocaine decrease the gel--liquid crystal phase transition temperature and increase the width of the phase transition of the dipalmitoylphosphatidylcholine (DPPC) model membrane. These effects roughly correlate with the efficiencies of the anesthetics to block action potential propagation in the nerves.

Anesthetics, Local↗
PubMed1983

A spin label study of the perturbation effect of tertiary amine anesthetics on brain lipid liposomes and synaptosomes.

The membrane disordering efficiency of four local anesthetics, including lidocaine, tetracaine, dibucaine and heptacaine (piperidinoethyl ester of 2-heptyloxyphenylcarbamic acid) has been studied by spin-labeling methods. The disordering efficiency of the drugs in rat total brain lipid liposomes was quantitated with the initial slope value of the order parameter versus drug concentration curve, the so-called change-in-order parameter value. Using the positional isomers of m-doxyl stearic acids (m = 5, 12 and 16), it has been demonstrated that the tested drugs reveal quite different disordering efficiency. There is a clear tendency of increasing disordering efficiency towards the methyl terminal of the lipid acyl chains. By a comparison of order parameter versus drug concentration and temperature at three depths of rat brain total lipid liposomes and synaptosomes, it is shown that the 'fluidizing effect' of local anesthetics does not correspond to fluidization of membrane by temperature and that tetracaine and dibucaine do not have equal disordering efficiency as judged by their solubility in the membrane. The disordering efficiency of these drugs on the hydrocarbone core of a membrane qualitatively corresponds to their anesthetic potency. Similar results were obtained in liposomes and synaptosomes. It is assumed that there is a similar incorporation of the local anesthetics in the liposomes and in the lipid part of synaptosomes.

Anesthetics, Local↗