ABSTRACT
Multifilamentary Bi2Sr2CaCu2Ox (Bi-2212) wire made by the powder-in-tube technique is the only high temperature superconductor made in the round shape preferred by magnet builders. The critical current density (J C ) of Bi-2212 round wire was improved significantly by the development of overpressure heat treatment in the past few years. Bi-2212 wire is commercially available in multiple architectures and kilometer-long pieces and a very promising conductor for very high field NMR and accelerator magnets. We studied the effects of precursor powder and heat treatment conditions on the superconducting properties and microstructure of recent Bi-2212 wires. Short samples of recent wire with optimized overpressure processing showed J C (4.2 K, 15 T) = 6640 A/mm2 and J C (4.2 K, 30 T) = 4670 A/mm2, which correspond to engineering critical current densities J E (4.2 K, 15 T) = 1320 A/mm2 and J E (4.2 K, 30 T) = 930 A/mm2.
ABSTRACT
Magnets are the principal market for superconductors, but making attractive conductors out of the high-temperature cuprate superconductors (HTSs) has proved difficult because of the presence of high-angle grain boundaries that are generally believed to lower the critical current density, J(c). To minimize such grain boundary obstacles, HTS conductors such as REBa2Cu3O(7-x) and (Bi, Pb)2Sr2Ca2Cu3O(10-x) are both made as tapes with a high aspect ratio and a large superconducting anisotropy. Here we report that Bi2Sr2CaCu2O(8-x) (Bi-2212) can be made in the much more desirable isotropic, round-wire, multifilament form that can be wound or cabled into arbitrary geometries and will be especially valuable for high-field NMR magnets beyond the present 1 GHz proton resonance limit of Nb3Sn technology. An appealing attribute of this Bi-2212 conductor is that, being without macroscopic texture, it contains many high-angle grain boundaries but nevertheless attains a very high J(c) of 2,500 A mm(-2) at 20 T and 4.2 K. The large potential of the conductor has been demonstrated by building a small coil that generated almost 2.6 T in a 31 T background field. This demonstration that grain boundary limits to high Jc can be practically overcome underlines the value of a renewed focus on grain boundary properties in non-ideal geometries.
ABSTRACT
Significant progress has been achieved in fabricating high-quality bulk and thin-film iron-based superconductors. In particular, artificial layered pnictide superlattices offer the possibility of tailoring the superconducting properties and understanding the mechanism of the superconductivity itself. For high-field applications, large critical current densities (J(c)) and irreversibility fields (H(irr)) are indispensable along all crystal directions. On the other hand, the development of superconducting devices such as tunnel junctions requires multilayered heterostructures. Here we show that artificially engineered undoped Ba-122/Co-doped Ba-122 compositionally modulated superlattices produce ab-aligned nanoparticle arrays. These layer and self-assemble along c-axis-aligned defects, and combine to produce very large J(c) and H(irr) enhancements over a wide angular range. We also demonstrate a structurally modulated SrTiO3(STO)/Co-doped Ba-122 superlattice with sharp interfaces. Success in superlattice fabrication involving pnictides will aid the progress of heterostructured systems exhibiting new interfacial phenomena and device applications.
ABSTRACT
The K- and Co-doped BaFe(2)As(2) (Ba-122) superconducting compounds are potentially useful for applications because they have upper critical fields (H(c2)) of well over 50 T, H(c2) anisotropy γ < 2and thin-film critical current densities J(c) exceeding 1 MA cm(-2) (refs 1-4) at 4.2 K. However, thin-film bicrystals of Co-doped Ba-122 clearly exhibit weak link behaviour for [001] tilt misorientations of more than about 5°, suggesting that textured substrates would be needed for applications, as in the cuprates. Here we present a contrary and very much more positive result in which untextured polycrystalline (Ba(0.6)K(0.4))Fe(2)As(2) bulks and round wires with high grain boundary density have transport critical current densities well over 0.1 MA cm(-2) (self-field, 4.2 K), more than 10 times higher than that of any other round untextured ferropnictide wire and 4-5 times higher than the best textured flat wire. The enhanced grain connectivity is ascribed to their much improved phase purity and to the enhanced vortex stiffness of this low-anisotropy compound (γ~1-2) when compared with YBa(2)Cu(3)O(7-x) (γ~5).
ABSTRACT
AIMS: Reticulon 3 (RTN3), a member of the reticulon family of proteins, interacts with the beta-secretase, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and inhibits its activity to produce beta-amyloid protein. The aim of the present study was to clarify the biological role of RTN3 in the brain and its potential involvement in the neuropathology of Alzheimer's disease (AD). METHODS: We performed immunohistochemical and biochemical analyses using a specific antibody against RTN3 to investigate the expression and subcellular localization of RTN3 in control and AD brain tissue samples. RESULTS: Western blot analysis revealed no significant differences in the RTN3 levels between control and AD brains. Immunohistochemical staining showed that RTN3 immunoreactivity was predominantly localized in pyramidal neurones of the cerebral cortex. The patterns of RTN3 immunostaining were similar in control and AD cerebral cortices, and senile plaques were generally negative for RTN3. Biochemical subcellular fractionation disclosed that RTN3 colocalized with BACE1 in various fractions, including the endoplasmic reticulum and the Golgi apparatus. Double-immunofluorescence staining additionally indicated that RTN3 was localized in both endoplasmic reticulum and Golgi compartments in neurones. CONCLUSIONS: These results show that RTN3 is primarily expressed in pyramidal neurones of the human cerebral cortex and that no clear difference of RTN3 immunoreactivity is observable between control and AD brains. Our data also suggest that there is considerable colocalization of RTN3 with BACE1 at a subcellular level.
Subject(s)
Alzheimer Disease/pathology , Brain/pathology , Carrier Proteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/metabolism , Amyloid Precursor Protein Secretases/metabolism , Animals , Aspartic Acid Endopeptidases/metabolism , Blotting, Western , Brain/metabolism , Endoplasmic Reticulum/metabolism , Female , Golgi Apparatus/metabolism , Humans , Immunohistochemistry , Male , Mice , Pyramidal Cells/metabolismABSTRACT
In order to develop a high current density in coils, Bi-2212 wires must be electrically discrete in tight winding packs. It is vital to use an insulating layer that is thin, fulfils the dielectric requirements, and can survive the heat treatment whose maximum temperature reaches 890 °C. A thin (20-30 µm) ceramic coating could be better as the insulating layer compared to alumino-silicate braided fiber insulation, which is about 100 µm thick and reacts with the Ag sheath during heat treatment, degrading the critical current density (Jc). At present, TiO2 seems to be the most viable ceramic material for such a thin insulation because it is chemically compatible with Ag and Bi-2212 and its sintering temperature is lower than the maximum temperature used for the Bi-2212 heat treatment. However, recent tests of a large Bi-2212 coil insulated only with TiO2 showed severe electrical shorting between the wires after over pressure heat treatment (OPHT). The origin of the shorting was frequent silver extrusions that penetrated the porous TiO2 layer and electrically connected adjacent Bi-2212 wires. To understand the mechanism of this unexpected behaviour, we investigated the effect of sheath material and hydrostatic pressure on the formation of Ag extrusions. We found that Ag extrusions occur only when TiO2-insulated Ag-0.2%Mg sheathed wire (Ag(Mg) wire) undergoes OPHT at 50 bar. No Ag extrusions were observed when the TiO2-insulated Ag(Mg) wire was processed at 1 bar. The TiO2-insulated wires sheathed with pure Ag that underwent 50 bar OPHT were also free from Ag extrusions. A key finding is that the Ag extrusions emanating from the Ag(Mg) sheath actually contain no MgO, suggesting that local depletion of MgO facilitates local, heterogeneous deformation of the sheath under hydrostatic overpressure. Our study also suggests that predensifying the Ag(Mg) wire before insulating it with TiO2 and doing the final OPHT can potentially prevent Ag extrusion.
ABSTRACT
Magnetic susceptibility, electrical resistivity, and heat capacity results are reported for the chemical substitution series URu2Si2-x P x for [Formula: see text]. This study expands in detail on work recently reported in Gallagher et al (2016 Nat. Commun. 10712), which focused on the small x region of this substitution series. Measurements presented here reveal persistent hybridization between the f- and conduction electrons and strong variation of the low temperature behavior with increasing x. Hidden order and superconductivity are rapidly destroyed for [Formula: see text] and are replaced for [Formula: see text] by a region with Kondo coherence but no ordered state. Antiferromagnetism abruptly appears for [Formula: see text]. This phase diagram differs significantly from those produced by most other tuning strategies in URu2Si2, including applied pressure, high magnetic fields, and isoelectronic chemical substitution (i.e. Ru â Fe and Os), where hidden order and magnetism share a common phase boundary. Besides revealing an intriguing evolution of the low temperature states, this series provides a setting in which to investigate the influence of electronic tuning, where probes that are sensitive to the Fermi surface and the symmetry of the ordered states will be useful to unravel the anomalous behavior of URu2Si2.
ABSTRACT
A main challenge that significantly impedes REBa2Cu3Ox (RE = rare earth) coated conductor applications is the low engineering critical current density J e because of the low superconductor fill factor in a complicated layered structure that is crucial for REBa2Cu3Ox to carry supercurrent. Recently, we have successfully achieved engineering critical current density beyond 2.0 kA/mm2 at 4.2 K and 16 T, by growing thick REBa2Cu3Ox layer, from â¼1.0 µm up to â¼3.2 µm, as well as controlling the pinning microstructure. Such high engineering critical current density, the highest value ever observed so far, establishes the essential role of REBa2Cu3Ox coated conductors for very high field magnet applications. We attribute such excellent performance to the dense c-axis self-assembled BaZrO3 nanorods, the elimination of large misoriented grains, and the suppression of big second phase particles in this ~3.2 µm thick REBa2Cu3Ox film.
ABSTRACT
The heavy fermion intermetallic compound URu2Si2 exhibits a hidden-order phase below the temperature of 17.5 K, which supports both anomalous metallic behavior and unconventional superconductivity. While these individual phenomena have been investigated in detail, it remains unclear how they are related to each other and to what extent uranium f-electron valence fluctuations influence each one. Here we use ligand site substituted URu2Si(2-x)P(x) to establish their evolution under electronic tuning. We find that while hidden order is monotonically suppressed and destroyed for x≤0.035, the superconducting strength evolves non-monotonically with a maximum near x≈0.01 and that superconductivity is destroyed near x≈0.028. This behavior reveals that hidden order depends strongly on tuning outside of the U f-electron shells. It also suggests that while hidden order provides an environment for superconductivity and anomalous metallic behavior, it's fluctuations may not be solely responsible for their progression.
ABSTRACT
The effects of ionophores, which can carry alkali metal cations, on platelet aggregation were examined. At an alkaline extracellular pH, alkali metal cation/H+ exchanger nigericin accelerated aggregation in K+-enriched medium, whereas it rather inhibited aggregation in Na+-enriched medium, even though the intracellular pH was only slightly alkaline. The inhibitory effect of Na+ on platelet aggregation was more clearly shown with the alkali metal cation exchanger gramicidin D. The ionophore had no effect or a slightly accelerative effect on aggregation in K+-enriched medium, whereas it significantly inhibited aggregation induced by thrombin, ADP and platelet activating factor in Na+-enriched medium. Fluorescence studies on fura-2-labeled platelets revealed that in Na+-enriched medium gramicidin D inhibited agonist-induced Ca2+ mobilization both in the presence and absence of extracellular Ca2+. These results suggest that the intracellular Na+ inhibits platelet aggregation by inhibiting Ca2+ mobilization.
Subject(s)
Calcium/blood , Platelet Aggregation , Sodium/physiology , Animals , Blood Platelets/drug effects , Blood Platelets/metabolism , Carrier Proteins/blood , Cattle , Cytosol/metabolism , Gramicidin/pharmacology , Hydrogen-Ion Concentration , In Vitro Techniques , Nigericin/pharmacology , Platelet Aggregation/drug effects , Potassium/physiology , Sodium-Calcium ExchangerABSTRACT
The effects of monovalent cations-inorganic alkali metal cations and organic quaternary ammonium cations-and monovalent inorganic anions on ADP-induced aggregation of bovine platelets were investigated. In the presence of K+, Rb+, Cs+, choline or tetramethylammonium, aggregation proceeded. However, aggregation was markedly restricted in media containing Li+, Na+, tetrabutylammonium or dimethyldibenzylammonium. With anions, aggregation proceeded in the order Cl- greater than Br- greater than I- greater than ClO4- greater than SCN-. The effects of cations significantly depended on Ca2+ concentration, whereas those of the anions depended little on Ca2+. Anions such as SCN- and ClO4- markedly decreased the fluorescence of the surface charge probe 2-p-toluidinyl-naphthalene-6-sulfonate, whereas cations had less pronounced effects. The relative effects of the anions on the fluorescence were consistent with their relative inhibitory effects on aggregation. These results suggest that inhibition of platelet aggregation by the anions is due to a change in the surface change of the platelet plasma membrane. On the other hand, kinetic analysis suggests that the effects of monovalent cations on platelet aggregation are due to their competition with Ca2+ during the process of aggregation.
Subject(s)
Adenosine Diphosphate/pharmacology , Platelet Aggregation/drug effects , Animals , Anions , Binding, Competitive , Blood Platelets/drug effects , Blood Platelets/metabolism , Calcium/pharmacology , Cations, Monovalent , Cattle , In Vitro Techniques , Kinetics , Membrane Potentials/drug effectsABSTRACT
The effects of long-chain cis-unsaturated fatty acids with different alkyl chain lengths and different numbers of double bonds on aggregation of bovine platelets and membrane fluidity were investigated. All the cis-unsaturated fatty acids tested inhibited aggregation and at the same time increased membrane fluidity in accordance with their inhibitory effects. The saturated fatty acids and trans-unsaturated fatty acid tested for comparison had much lower or no effects on aggregation and membrane fluidity. The inhibitory effects of mono cis-unsaturated fatty acids increased with increase of their alkyl chain length. cis-Unsaturated fatty acids with two or more double bonds had more inhibitory effects than mono-unsaturated fatty acids. The position of the double bonds had less influence than the number of double bonds. We also examined the effects of cis-unsaturated fatty acids on membrane fluidity with diphenylhexatriene and anthroyloxy derivatives of fatty acids as probes and observed increased fluidity to be considerable in the membrane. The alcohol analogs of cis-unsaturated fatty acids also inhibited aggregation and increased membrane perturbation. These results suggest that the inhibition of platelet aggregation by cis-unsaturated compounds is due to perturbation of the lipid layer.
Subject(s)
Fatty Acids, Unsaturated/pharmacology , Fatty Alcohols/pharmacology , Membrane Fluidity/drug effects , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Animals , Cattle , Fluorescence Polarization , TemperatureABSTRACT
The in vitro inhibitory effects of cis-polyunsaturated fatty acids, linolenic (18:2 delta 9,12), alpha-linoleic (18:3 delta 9,12,15) and eicosatrienoic (20:3 delta 11,14,17) acid, on bovine platelet aggregation and their inhibitory mechanism were investigated. These fatty acids inhibited platelet aggregation induced by ADP and thrombin to similar extent. Fluorescence analyses with fura-2-loaded platelets showed that, in the concentration ranges that inhibited aggregation, they also inhibited agonist-induced increase in cytoplasmic Ca2+. According to radioimmunoassay study, addition of these fatty acids increased cyclic AMP contents in the presence of theophylline corresponded with their inhibitory effects on aggregation. These fatty acids induced a 1.6-1.8-fold increase over basal concentration of cyclic AMP in the concentration ranges that fully inhibited aggregation. On the other hand, saturated fatty acid, stearic acid, affected neither aggregation nor cyclic AMP levels. As reported previously [1985) Biochim. Biophys. Acta 818, 391), these unsaturated fatty acids induced increase in membrane fluidity in the same concentration range. These results suggest that inhibition of platelet aggregation by cis-polyunsaturated fatty acids is due to the increase in cyclic AMP levels. This increase seems to be due to stimulation of adenylate cyclase which is mediated by membrane perturbation.
Subject(s)
Calcium/metabolism , Cyclic AMP/metabolism , Fatty Acids, Unsaturated/pharmacology , Membrane Fluidity/drug effects , Platelet Aggregation Inhibitors , 8,11,14-Eicosatrienoic Acid/pharmacology , Adenylyl Cyclases/metabolism , Animals , Cattle , Cells, Cultured/drug effects , Cytoplasm/metabolism , Dose-Response Relationship, Drug , Fluorescence Polarization , Linoleic Acid , Linoleic Acids/pharmacology , Linolenic Acids/pharmacology , Platelet Aggregation/drug effects , Stearic Acids/pharmacology , StereoisomerismABSTRACT
The effect of nigericin on aggregation of bovine platelets was investigated in media containing the chloride salts of various alkali metal cations of quaternary ammonium cations. In medium with K+, which has the highest permeability with the ionophore among the cations tested, nigericin slightly enhanced both ADP- and thrombin-induced aggregation. In medium with Na+, nigericin scarcely affected ADP-induced aggregation, and slightly inhibited thrombin-induced aggregation. In media with Cs+, choline and tetramethylammonium, it inhibited the aggregations induced by both ADP and thrombin. Measurement of the cytoplasmic pH with the fluorescent probe 2',7'-bis(carboxyethyl)5,6-carboxyfluorescein showed that nigericin increased the intracellular pH in K+ medium and caused its stable decrease (of about 0.6) in Cs+, choline and tetramethylammonium media, but caused only a small transient decrease in medium with Na+. These results suggest that the effects of nigericin on platelet aggregation are mainly due to its effects on the cytoplasmic pH. This conclusion is supported by the findings that the effects on platelet aggregation of other types of ionophore tested were also proportional to their effects on the cytoplasmic pH.
Subject(s)
Anti-Bacterial Agents/pharmacology , Blood Platelets/physiology , Cations , Nigericin/pharmacology , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Animals , Blood Platelets/drug effects , Cattle , Cesium/pharmacology , Choline/pharmacology , Cytoplasm , Gramicidin/pharmacology , Hydrogen-Ion Concentration , Potassium/pharmacology , Quaternary Ammonium Compounds/pharmacology , Sodium/pharmacology , Thrombin/pharmacology , Valinomycin/pharmacologyABSTRACT
The effects of four types of reagents--a stimulant analog (ATP), reagents increasing cAMP (theophylline and (-)-isoproterenol), Ca2+ blockers (chlorpromazine, procaine, dibucaine and tetracaine) and nonspecific membrane-reactive reagents (n-butanol, n-hexanol and linoleate) - on ADP-induced Ca2+ mobilization and aggregation of platelets were investigated. All the reagents tested inhibited the aggregation. Of these reagents, those increasing cAMP and the stimulant analog inhibited the aggregation at least partly by inhibiting Ca2+ mobilization, whereas Ca2+ blockers and nonspecific membrane-reactive reagents must have inhibited the aggregation by different mechanisms, because they had: (1) no effect on ADP-induced Ca2+ mobilization, (2) accelerated it, or (3) themselves stimulated Ca2+ mobilization. The results showed that the inhibitory effects of Ca2+ blockers were at least partly due to competition with Ca2+ for binding sites on the outside of the membrane, whereas the effects of the nonspecific membrane-reactive reagents tested were due to membrane perturbation.
Subject(s)
Adenosine Diphosphate/pharmacology , Adenosine Triphosphate/pharmacology , Blood Platelets/physiology , Calcium Channel Blockers/pharmacology , Calcium/pharmacology , Platelet Aggregation/drug effects , Alcohols/pharmacology , Animals , Blood Platelets/drug effects , Cattle , Cell Membrane/drug effects , Cell Membrane/physiology , Cyclic AMP/blood , Isoproterenol/pharmacology , Kinetics , Linoleic Acid , Linoleic Acids/pharmacology , Theophylline/pharmacologyABSTRACT
The inhibitory effects of saturated fatty acids with 4 to 18 carbon atoms on ADP-induced aggregation of bovine platelets were investigated. The inhibitory effects of the acids increased with increase of their alkyl chain length up to C14. On the other hand, from C16 the inhibitory effects tended to decrease with increase of chain length, and stearic acid (C18) was not inhibitory. There was a linear relationship between the inhibitory effects and alkyl chain lengths up to C12. This linear relation and the slope of the linear regression line suggested that the inhibitory effects of the acids depended on their partition into the membrane. The fatty acids decreased the fluorescence of the surface charge probe 2-p-toluidinylnaphthalene-6-sulfonate, indicating that they increased the negative charge on the membrane surface. The relative effects of the acids on the fluorescence were consistent with their relative inhibitory effects on aggregation. These results suggest that the inhibition of platelet aggregation by saturated fatty acids is due to a change in the membrane surface charge of the platelet plasma membrane.
Subject(s)
Adenosine Diphosphate/pharmacology , Fatty Acids/pharmacology , Platelet Aggregation/drug effects , Animals , Cattle , Fluorescence Polarization , Mathematics , Membrane Fluidity/drug effects , Membrane Potentials/drug effectsABSTRACT
The effects of long-chain unsaturated fatty acids such as linoleic acid on bovine platelets were examined. Not only linoleic acid, but also oleic and linolenic acid, at just below the concentrations causing marked cell lysis, induced an absorbance decrease of the platelet suspension in the presence of Ca2+. Since this absorbance decrease was reversed by the addition of EDTA and moreover aggregate formation was found by macroscopic and microscopic observation, it was concluded that unsaturated fatty acids at just below their lytic concentrations caused platelet aggregation. Unsaturated fatty acids also caused release of adenine nucleotides, but there was a lag time between the release and the aggregation, just as with ADP-induced release, suggesting that the aggregation was independent of the release of ADP. It was revealed that this activation of platelets by unsaturated fatty acids was caused by marked Ca2+ uptake into the cytoplasm, resulting from significant membrane perturbation.
Subject(s)
Blood Platelets/drug effects , Fatty Acids, Unsaturated/pharmacology , Adenosine Triphosphate/metabolism , Animals , Calcium/pharmacology , Cattle , Cell Survival/drug effects , Colforsin , Diterpenes/pharmacology , Edetic Acid/pharmacology , Fluorescence Polarization , Linoleic Acid , Linoleic Acids/pharmacology , Membrane Fluidity/drug effects , Platelet Aggregation/drug effects , Tetracaine/pharmacologyABSTRACT
Four spin-labeled probes (5-doxylstearic acid (5-NS), its methyl ester (5-NMS), 16-doxylmethylstearate (16-NMS) and 4-(N,N-dimethyl-N-pentadecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-ox yl (CAT-15)) were used to monitor membrane fluidity change in bovine platelets induced by three alkyl alcohols, benzyl alcohol and two phenolic compounds. The relationship between the increase in membrane fluidity induced by these compounds and their inhibitory effects on platelet aggregation was observed. Experiments with the four probes showed that n-hexyl alcohol induced decreases in the order parameter of 5-NS and apparent rotational correlation times of the other probes at the same minimal alcohol concentration. The decreases were observed in the concentration range that inhibited aggregation. n-Amyl alcohol and n-butyl alcohol decreased the values of the parameters of the above mentioned only at higher concentrations that were dependent on their hydrophobicities. Like alkyl alcohols, benzyl alcohol and phenolic compounds decreased the values of the parameters in the concentration ranges in which these compounds inhibited platelet aggregation. The concentration of these compounds causing 50% inhibition of platelet aggregation, the IC50 values, and data on 5-NS-labeled platelets indicated that they inhibited aggregation and decreased the value of the order parameter at lower concentrations relative to their Poct values in comparison to the effective concentrations of alcohols. Phenolic compounds also decreased the values of the apparent rotational correlation times of 5-NMS and 16-NMS. These results indicate that the inhibition of platelet aggregation by alcohols and phenolic compounds is due to membrane perturbation in wide range in depths within the lipid bilayer.
Subject(s)
Alcohols/pharmacology , Blood Platelets/metabolism , Membrane Fluidity/drug effects , Phenols/pharmacology , Platelet Aggregation Inhibitors , Platelet Aggregation/drug effects , Animals , Blood Platelets/drug effects , Cattle , Electron Spin Resonance Spectroscopy/methods , Kinetics , Mathematics , Models, Biological , Spin Labels , Structure-Activity RelationshipABSTRACT
The inhibitory effects of alkyltrimethylammonium ions on ADP- and thrombin-induced aggregation of bovine platelets were investigated. The ammonium cations inhibited the two aggregation reactions to similar extents. The relationship between their inhibitory effects on ADP-induced aggregation and their alkyl chain lengths from C8 to C18 was investigated. Results showed that the inhibitory effects of ammonium cations increased with increase of their alkyl chain lengths up to C16, and that the increase was linear with chain lengths of up to C14. This linear relation and slope of the linear regression line suggested that the inhibitory effects of the ammonium cations depended on their partitioning into the membrane. However, unlike long-chain unsaturated fatty acids, they did not affect the membrane fluidity of the platelets. Fluorescence analysis of fura-2 loaded platelets revealed that, in the concentration range where the alkyltrimethylammonium ions inhibited aggregation, they inhibited agonist-induced increase in cytosolic Ca2+ both in the presence and absence of extracellular Ca2+. These results suggest that inhibition of platelet aggregation by alkyltrimethylammonium ions is mainly due to their inhibition of increase in cytoplasmic Ca2+ by inhibition of both intracellular Ca2+ mobilization and Ca2+ uptake.
Subject(s)
Blood Platelets/metabolism , Calcium/metabolism , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Quaternary Ammonium Compounds/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Biological Transport/drug effects , Blood Platelets/drug effects , Cattle , Cytosol/metabolism , Membrane Fluidity/drug effects , Molecular Weight , Thrombin/pharmacologyABSTRACT
The effects of phenol derivatives on aggregation of bovine platelets induced by ADP, thrombin, platelet activating factor, collagen and A23187 were investigated. The phenol derivatives inhibited all these induced aggregations except that by the calcium ionophore. The derivatives each inhibited the aggregations induced by ADP, thrombin, platelet activating factor and collagen, respectively, within a similar concentration range. A linear relation was found between the inhibitory potencies of the phenol derivatives and their partition coefficients between n-octanol and water (Poct values), suggesting that their interaction with hydrophobic regions of the cell was important for inhibition. Fluorescence analyses with fura-2-loaded platelets showed that in the concentration ranges in which the phenol derivatives inhibited aggregation, they also inhibited agonist-induced increases in Ca2+ both in the presence and absence of extracellular Ca2+. Moreover, a high correlation was found between the inhibitory effects of the derivatives on aggregation and their effects on Ca2+ mobilization. These results suggest that inhibition of platelet aggregation by phenol derivatives is mainly due to inhibition of the increase in cytoplasmic Ca2+ by inhibition of both intracellular Ca2+ mobilization and Ca2+ uptake.