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Biomedical subjects

R Nosál

Publications and source records attributed to R Nosál.

At least 19 recordsLinked to original sources
PubMed2000

Platelet-dependent modulation of polymorphonuclear leukocyte chemiluminescence.

Human blood platelets decreased luminol-enhanced chemiluminescence of human polymorphonuclear leukocytes (PMNL) stimulated with FMLP or Ca2+-ionophore A23187 by 56 or 47%, respectively. Horseradish peroxidase potentiated the decreasing effect of platelets on A23187-stimulated PMNL (92% inhibition) or reversed inhibition of FMLP-induced chemiluminescence to 94% potentiation, indicating dependence of platelet activity on availability of extracellular peroxidase. Moreover, platelet activity may depend also on the extent of platelet activation, as non-activated platelets (in the presence of FMLP) were found to potentiate PMNL-generated chemiluminescence, while platelets activated with A23187 displayed the opposite effect. Interference of platelets with formation and liberation of superoxide anion was indicated by platelet-modified isoluminol chemiluminescence. Superoxide dismutase with catalase and sodium azide were used, respectively, to differentiate the intracellular and the extracellular part of the chemiluminescence signal. Platelets were found to be capable of modifying both components of chemiluminescence, i.e., oxygen metabolites produced on the plasma membrane as well as on membranes of intracellular granules.

Adult↗
PubMed2000

Human blood platelets, PMN leukocytes and their interactions in vitro. Responses to selective and non-selective stimuli.

Using simultaneous recording of aggregation and chemiluminescence, responses of human polymorphonuclear leukocytes, blood platelets and their mixture were investigated after stimulation by specific as well as non-specific stimuli for each cell. In our experimental settings, aggregation of platelets and PMN leukocytes was increased in the following order of stimuli: PMA<A23187<thrombin and FMLP<A23187<PMA, respectively. FMLP selective for PMN leukocytes did not activate platelet aggregation, and, on the other hand, aggregation of PMN leukocytes was not induced by thrombin. The presence of PMN leukocytes decreased aggregatory responses of platelets to all the stimuli applied. Luminol amplified chemiluminescence of PMN leukocytes was increased in the order: thrombin<FMLP<A23187<PMA, but platelets alone did not show detectable chemiluminescence response to any stimulation. Platelets significantly decreased chemiluminescence of PMN leukocytes and their inhibitory effect did not depend on the type of stimulation. These observations suggest that under defined experimental conditions human PMN leukocytes and platelets might decrease mutually their dominant responses in vitro. The inhibitory effect was dependent either on the selectivity of stimuli, or on cell to cell contact before stimulus addition.

Adult↗
PubMed1999

Aggregation of human blood platelets in the presence of the pyridoindole stobadine.

The antiarrhythmic and cardioprotective drug stobadine, possessing antioxidant and neuroprotective properties, was studied as to its in vitro effect on aggregation of human blood platelets. Pretreatment of platelets with stobadine for 30 s inhibited stimulated platelet aggregation in a dose-dependent way. Depending on the aggregation stimulus used, the minimal effective concentrations of the drug were 1 micromol/l (adrenaline), 200 micromol/l (ADP), and 1,000 micromol/l (PMA). Aggregation induced with thrombin or Ca2+-ionophore A23187 was not changed in the presence of stobadine even in the concentration of 1,000 micromol/l. Addition of stobadine 30 s after adrenaline was also effective and terminated aggregation (100 and 1,000 micromol/l) or prolonged onset of its second phase (10 micromol/l). The presented experiments showed stobadine as a potent inhibitor of adrenaline-induced aggregation, indicating its involvement in the observed antithrombotic and cytoprotective activity.

Antioxidants↗
PubMed1999

Effect of stobadine on oxygen free radical generation in stimulated human polymorphonuclear leukocytes.

The generation both superoxide and a mixture of reactive oxygen species was recorded in a suspension of human polymorphonuclear leukocytes stimulated with phorbol myristate acetate. While stobadine dose-dependently decreased chemiluminescence, only its highest concentration used reduced significantly superoxide generation. The results suggest that stobadine is a more effective scavenger of free radicals rather than a quencher of superoxide anion.

Antioxidants↗
PubMed1999

Effect of stobadine on human stimulated polymorphonuclear leukocytes.

The effect of stobadine (0.1-100 microM) on human polymorphonuclear (PMN) leukocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine, a specific receptor activator, or with the calcium ionophore, A-23187 (receptor bypassing stimulus) was investigated with respect to: i) superoxide generation, ii) beta-glucuronidase release and iii) 3[H]-arachidonic acid liberation. Stobadine was found to exert an inhibitory effect on N-formyl-methionyl-leucyl-phenylalanine but not on A-23187-stimulated PMN leukocytes. The effect was more intensive on superoxide generation and beta-glucuronidase release than on 3[H]-arachidonic acid liberation. These results indicate that the inhibitory effect of stobadine is most probably via a mechanism dependent on signal transduction across the plasma membrane. This effect may occur through inhibition of arachidonate signal transduction through a regulatory G-protein.

Antioxidants↗
PubMed1999

Nonreceptor interactions in the pharmacology of blood platelets.

On the basis of values corresponding to concentrations exhibiting 50% inhibition of platelet aggregation induced with different stimuli and 50% inhibition of arachidonic acid liberation and thromboxane generation, we compared the antiplatelet effect of two cationic amphiphilic drugs--chloroquine and dithiaden. Compared to chloroquine, dithiaden was much more effective in inhibiting platelet aggregation, A-23187 induced arachidonic acid liberation and thromboxane generation. Chloroquine, on the other hand, was more effective in the inhibition of thrombin-induced arachidonic acid liberation.

Adult↗
PubMed1998

Potentiation of the discriminative-stimulus effects of methamphetamine by the histamine H3 receptor antagonist thioperamide in rats.

In order to assess the role of histamine H3 receptors in the discriminative-stimulus effects of methamphetamine, rats were trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food presentation. The histamine H3 receptor antagonist thioperamide (1.0 mg/kg s.c.), which facilitates histamine release, significantly shifted the methamphetamine dose-response curve to the left when tested together with different doses of methamphetamine and markedly extended the time-course of methamphetamine's discriminative-stimulus effects. The histamine H3 receptor agonist R-alpha-methylhistamine (3.0 mg/kg i.p.), which blocks histamine release, did not produce any effects when given alone, but it attenuated the effects of thioperamide on the methamphetamine dose-response curve when both drugs were given together. Thus, methamphetamine's discriminative-stimulus effects are markedly potentiated by the blockade of histamine H3 receptors by thioperamide. This is likely due to thioperamide's actions at histamine H3 autoreceptors on histaminergic neurons to facilitate release of histamine by methamphetamine or at histamine H3 heteroreceptors on other monoaminergic neurons (e.g., dopaminergic, serotonergic or noradrenergic) to facilitate release of other neurotransmitters.

Animals↗
PubMed1996

Inhibition of blood platelet functions by cationic amphiphilic drugs in relation to their physico-chemical properties.

The effects of bromadryl, dithiaden, chloroquine and propranolol on thrombin-stimulated rat platelet aggregation (measured turbidimetrically) and thromboxane B2 generation (detected by an RIA method) were compared with four selected physico-chemical parameters of these drugs. Platelet aggregation was inhibited in the rank order of potency: bromadryl > dithiaden > propranolol > chloroquine, which corresponded with the decrease in the net charge of the terminal methyl-(or ethyl-) groups in the side chain and with the increase of the dipole moment of drug molecules. On the other hand, the rank order of potency in which the drugs tested inhibited thromboxane B2 formation (chloroquine > dithiaden > bromadryl > propranolol) correlated well with the decline in molar refractivity of the drugs. No relationship was found between inhibitory effects of drugs and their partition coefficients. The results presented indicate that inhibition of platelet functions might consist of several types of drug-cell interactions, depend on the structure and physico-chemical properties of the drugs and cannot be estimated simply on the basis of partition coefficients.

Animals↗
PubMed1996

Human polymorphonuclear leukocytes: effect of chloroquine on aggregation, arachidonic acid liberation and thromboxane B2 generation.

The effects of the antimalarial drug chloroquine (CQ) on arachidonic acid (AA) liberation from, thromboxane B2 (TXB2) formation in, and aggregation of isolated human polymorphonuclear (PMN) leukocytes stimulated with N-formyl-methionyl-leucyl-phenyl-alanine (FMLP) were investigated. CQ decreased aggregation of stimulated PMN leukocytes, however in contrast to AA liberation and TXB2 formation, lower concentrations were more effective than the highest one used. This effect may be associated with an increase in intracellular pH, reported to be induced by higher CQ concentrations, possibly counteracting the inhibition of aggregation, and/or eliminating negative feed back control of aggregation by lack of prostaglandins.

Arachidonic Acid↗
PubMed1995

Chloroquine inhibits stimulated platelets at the arachidonic acid pathway.

Chloroquine inhibited arachidonic acid liberation from membrane phospholipids of thrombin- and A23187- stimulated platelets. In addition, it dose-dependently inhibited stimulated malondialdehyde formation and thromboxane B2 generation in the same platelets. The linear correlation between the inhibition of arachidonic acid liberation and malondialdehyde formation indicated that chloroquine inhibited activated phospholipase A2 in thrombin-stimulated platelets, similarly as it does in different cells and tissues. Yet, the nonlinear relationship between arachidonic acid liberation along with malondialdehyde formation and thromboxane generation as well as aggregation suggest that phospholipase A2 does not seem to be the only site of chloroquine action. Rather, it may affect platelets either at other levels of the arachidonic acid cascade too, or at some different stimulatory pathways, like intraplatelet calcium mobilisation, phosphoinositide cycle, calmodulin and protein kinase C activation.

Animals↗