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Biomedical subjects

V Klenerová

Publications and source records attributed to V Klenerová.

At least 19 recordsLinked to original sources
PubMed2005

Effects of stress and of amphetamine on passive avoidance conditioning in rats.

This study examined the effects of immobilization stress combined with water immersion (ICS) and/or amphetamine (AM) on different memory phases in the passive avoidance task in rats. The performance of rats was evaluated in the retention tests 24 and 48 h after a single acquisition trial. ICS exposure lasting 1 h impaired retention of the learned avoidance response if applied 2 to 4 h before or immediately after training. The stressor did not affect retrieval if presented 5 or 2 h before the retention test. AM was used i.p. at the dose of 8 or 1 mg/kg. Neither 8 mg AM administered 4 h before nor 8 or 1 mg doses given after training did not impair the retention performance in unstressed rats. The 1 mg AM prevented the impairment of retention in animals exposed to the stressor 3 or 4 h before training but had no effect when the stronger impairment was induced by ICS 2 h before training. However, when given 1 h before retention testing, 1 mg AM attenuated even the severe impairment induced by the pre-training stressor exposure. Our results suggest that ICS impairs primarily the early phase of memory consolidation and a low dose of AM can prevent this effect.

Amphetamines↗
PubMed2004

In situ detection of cyclic AMP-phosphodiesterase activity in the heart of Lewis and Sprague-Dawley rats: the effect of restraint stress or amphetamine application.

Cyclic AMP plays an important role in heart functions under normal as well as pathological conditions. Since phosphodiesterase (PDE), responsible for the hydrolysis of cAMP, is equally important as synthesizing adenylyl cyclase, we decided to determine its activity by cytochemical procedure after exposure of rats to restraint stress or an acute dose of amphetamine. Sprague-Dawley (S-D) and Lewis (LE) rats, the latter known to have a deficient hypothalamo-pituitary-adrenal axis activity, were used in order to disclose the possible significance of rat strain on PDE activity. Animals were divided into 3 groups: controls, rats treated with an acute dose of amphetamine (8 mg/kg, i.p., for 60 min) and rats under restraint stress for 60 min. Control hearts of both strains revealed PDE activity on sarcolemma of cardiomyocytes and plasmalemma of endothelial cells of microvessels. In LE rats we observed an additional enzyme reaction in junctional sarcoplasmic reticulum. In addition, cardiomyocytes of LE rats revealed a higher PDE activity when compared to S-D rats. Restraint stress decreased PDE activity in cardiomyocytes of LE rats while amphetamine markedly inhibited enzyme activity in cardiomyocytes of S-D rats. Endothelial PDE was more resistant to stress. Our results indicate differences in PDE localization and variations in sensitivity of myocardial cAMP-PDE of LE and S-D rat strains to restraint stress and amphetamine application.

Amphetamines↗
PubMed2003

Exposure to intermittent high altitude induces different changes in adenylyl cyclase activity in hearts of young and adult Wistar rats.

This study investigates changes of adenylyl cyclase activity in the heart of young and adult Wistar rats exposed to experimental conditions simulating high altitude hypoxia as a model for interpretation of some adaptive changes of adenylyl cyclase observed in human. The exposure of rats to intermittent high altitude (IHA) hypoxia (5000 m) showed significant adaptive changes. The right ventricular weight and the ratio of right/left ventricular weights of adult rats exposed to IHA were significantly increased when compared to appropriate controls; adaptive changes of cardiac adenylyl cyclase being dependent on the age of the animals. The isoprenaline-stimulated activity was higher in the left than in the right ventricle, and in both ventricles it was higher in young rats than in adult rats. When compared to controls, isoprenaline stimulation was decreased in the right ventricles of adapted young rats and, by contrast, it was increased in the left ventricles of adapted adult rats. This decrease and increase of adenylyl cyclase activity evoked by isoprenaline was paralleled by forskolin-induced adenylyl cyclase activity in these experimental groups. It seems therefore that the changes in the pattern of total adenylyl cyclase activity observed under IHA hypoxia may at least be partially explained by the changes of beta-adrenergic receptor susceptibility following IHA hypoxia.

Adaptation, Physiological↗
PubMed2003

Impaired passive avoidance acquisition in Wistar rats after restraint/cold stress and/or stresscopin administration.

Stresscopin (SCP) and related peptides are new members of the corticotropin-releasing factor (CRF) peptide family that are selective ligands for CRF type 2 receptor; these ligands are essential for maintaining homeostasis after stress. SCP (i.p. injections) was tested on the passive avoidance learning task in stressed Wistar rats; it impaired the formation of memory trace. The retention performance deficit induced by SCP was comparable with the deficit induced by the stressor of restraint/cold. More profound impairment of avoidance response occurred following combined application of SCP and stressor. More specific actions of SCP can be expected from its studies with targeted intracerebral applications.

Animals↗
PubMed2001

[Nobel Prize winning laureates in physiology or medicine for the year 2000--a few comments on discoveries related to signal transduction].

The Nobel Assembly awarded The Nobel Prize in Physiology or Medicine for 2000 jointly to Arvid Carlsson, Paul Greengard and Eric Kandel for their discoveries concerning signal transduction in the nervous system. On the examples of their predecessors we attempted to demonstrate how results of basic research serve as building blocks for new discoveries and for the application of research results into the praxis. We presented not only the basic discoveries of laureates of Nobel Prize for year 2000 (biological role of dopamine, regulation of cell functions by phosphorylation of proteins, changes in transduction of signals during processes of memory), but we also mentioned previous discoveries that helped in the research of the last laureates. These discoveries concerned not only the storage and metabolism of transmitters, formulation of the concept of cyclic AMP as a second messenger of hormonal action, the role of G-proteins in transduction processes in receptor-effector complexes, processes of phosphorylation of proteins as regulators of cell functions, but we also mentioned the discovery of other second messengers and substances functioning as local hormones (prostaglandins and related compounds). Most of the described discoveries have not only the value as stones that can help to fill still incomplete mosaic of our present knowledge, but they also represent the immediate basis for the development and use of very important remedies, such as are antiparkinsonics, antidepressive drugs, nonsteroidal antiinflammatory drugs, etc.

History, 20th Century↗
PubMed1999

Effects of immobilization stress combined with water immersion and chronic amphetamine treatment on the adenylyl cyclase activity in rat neurohypophysis.

Several papers have indicated the participation of cyclic AMP as a second messenger for the release of neurohypophysial hormones. Since very little is known about the effects of stress and drugs of abuse on this process, we studied the activity of adenylyl cyclase in the neurohypophyses after immobilization stress and chronic amphetamine treatment. Our findings indicate the involvement of cyclic AMP in the regulation of neurohypophysis as well as the increase in total adenylyl cyclase both after application of immobilization stress combined with water immersion and after chronic amphetamine treatment.

Adenylyl Cyclases↗
PubMed1998

Different activity of adenylyl cyclase in prefrontal cortex in three rat strains. The effect of amphetamine.

Since the literature data do not provide enough information on the effects of amphetamine on the prefrontal cortex and since many controversial findings were reported in various rat strains we decided to compare adenylyl cyclase activity in the prefrontal cortex in various rat strains and test the effects of chronic amphetamine treatment (for 14 days) on the activity of this enzyme. Basal adenylyl cyclase activity was lower in Wistar rats than in Sprague-Dawley and Lewis rat strains. Amphetamine treatment produced in Wistar rats a substantial decrease in basal adenylyl cyclase activity. In Sprague-Dawley rats, we observed the highest enzyme activity which was slightly reduced after amphetamine treatment. In Lewis rats which had basal activity close to the activity of Wistar rats, amphetamine produced an increase in enzyme activity. The total adenylyl cyclase activity, estimated in the presence of forskolin, was the lowest in Wistar rats. The highest stimulation was observed in Lewis rats. Amphetamine treatment caused a very significant inhibition of total adenylyl activity in Wistar rats and a smaller inhibition in Sprague-Dawley rats. However, in Lewis rats amphetamine treatment increased the dose-response curve of forskolin stimulation. These results show that Lewis rats, compared to the other two strains, develop not only quantitatively but also qualitatively different responses.

Adenylyl Cyclases↗
PubMed1995

Sigma ligands indirectly modulate the NMDA receptor-ion channel complex on intact neuronal cells via sigma 1 site.

To investigate the modulatory effects of sigma ligands on the N-methyl-D-aspartate (NMDA) receptor-ion channel complex in vivo, we examined the intact cell binding of 3H-N-[1-(2-thienyl)cyclohexyl]piperidine (3H-TCP) to cultured neuronal cells prepared from fetal rat telencephalon. The 3H-TCP binding was saturable, reversible, and inhibited by a selective NMDA receptor antagonist, D-amino-5-phosphonovaleric acid. MII-limolar Mg2+ inhibited 3H-TCP binding both in the absence and presence of L-glutamate. 5-Methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK801) inhibited 3H-TCP intact cell binding in a competitive manner, while haloperidol inhibited it in a noncompetitive manner. The effect of the test drugs to inhibit 3H-TCP intact cell binding was in the order of dextromethorphan, haloperidol > (+/-)MK 801 > (+)pentazocine > (-)pentazocine > DTG > PCP > (+)-N-allylnormetazocine [(+)SKF 10047] > (+)3-(3-hydroxyphenyl)-N- (1-propyl)piperidine [(+)3-PPP] > (-)SKF 10047 > (-)3-PPP. The IC50 values of the six sigma ligands for 3H-TCP binding were closely correlated with the Ki values of the corresponding drugs for DTG site 1 in the guinea pig brain reported by Rothman et al. (1991). These findings suggest that the sigma ligand indirectly modulates the NMDA receptor ion channel complex, presumably through sigma 1 sites in vivo as well as in vitro.

2-Amino-5-phosphonovalerate↗
PubMed1995

Effects of pertussis toxin treatment of rats on estradiol-induced adenohypophyseal growth reaction and on adrenergic lipolysis.

After long-lasting administration of estradiol (4-6 weeks) in the presence or absence of pertussis toxin treatment we followed up the changes in body weight and adenohypophyseal weight in rats subjected to this treatment. The most striking effect was the potentiating effect of pertussis toxin on the estradiol-induced adenohypophyseal growth reaction. Adenylyl cyclase activity in the adenohypophysis was significantly increased in the estradiol-treated group and the addition of pertussis toxin did not further increase this enzyme activity. The lipolytic activity in adipose tissue exhibited a similar response as adenohypophyseal growth. Adrenergic lipolysis stimulated by pertussis toxin was highly significantly increased in tissues of rats treated with pertussis toxin. Our results show that the estrogen-induced adenohypophyseal growth reaction is highly potentiated by the treatment of rats with pertussis toxin and that this effect is in many aspects similar to that observed in adrenergic lipolysis. It thus seems that both processes might be mediated via a pertussis toxin-sensitive G protein which is involved in inhibitory regulation of adenylyl cyclase.

Adenylate Cyclase Toxin↗
PubMed1994

Changes in beta-adrenergic receptors in the neurohypophysis and intermediate lobe of rat hypophysis exposed to stress.

Changes in beta-adrenergic receptors in the neurohypophysis and intermediate lobe of the rat have been characterized under physiological and stress conditions. Classical immobilization stress (IMO) was also combined with the immersion of rats into water (IMO + COLD stress). Both types of stress were applied for 30, 60 or 150 min. The intensity of stress stimuli were controlled by measuring the level of plasma ACTH. Changes in the level of plasma ACTH indicate that both types of experimental protocol induced reliable and reproducible stress conditions. Binding studies dealing with beta-adrenergic receptors in the intermediate lobe and neurohypophysis were performed in saturation binding studies by using of 125I-iodopindolol. Binding parameters, maximal binding capacity (Bmax) and dissociation constant (Kd) were assessed by nonlinear analysis with computer program Viewfit. In the neurohypophysis, no changes of Kd were found in the stressed animals. However, maximal binding capacity was decreased significantly with the increased exposure to the stress. In the intermediate lobe Kd values were slightly decreased and Bmax values decreased gradually with increasing duration of stress exposure. Our findings suggest that the process of receptor desensitization of beta-adrenergic receptors can also be detected under stress conditions in the neurohypophysis and intermediate lobe of the pituitary gland where it could contribute to the mechanisms involved in stress reactions.

Adrenocorticotropic Hormone↗
PubMed1986

Graphical orientation procedure for the estimation of Kd and Bmax values of ligand binding to two receptor subpopulations.

Within a few minutes, the procedure described here provides to the investigator, performing binding studies, information about Kd and Bmax values of two possibly present receptor subpopulations. The procedure is based on the comparison of the experimental curve with values of ligand binding to only one receptor population at 4 defined levels of radioligand binding. The binding parameters are derived from comparison of 4 horizontal deviations at these levels with tabulated deviations. Kd and Bmax values can be further confirmed by comparison of the experimental data with the simulated binding curve obtained by entering the binding parameters found in the formula for ligand binding to two receptor subpopulations. The practical use of this procedure was demonstrated both for simulated and for experimental data; it was confirmed by comparison with binding parameters obtained by computer programs used for the evaluation of receptor heterogeneity.

Kinetics↗
PubMed1986

A simple and rapid orientation procedure for the estimation of affinities (1/Kd) and maximum binding capacities (Bmax) of ligand binding to two receptor subpopulations.

This paper describes a simple and rapid procedure for the estimation of specific parameters (dissociation constants, Kd and maximum binding capacities, Bmax) of ligand binding to two receptor subpopulations. This procedure provides, in a few minutes, the investigator, performing the actual binding studies, the necessary information about receptor heterogeneity, enabling the investigator to plan further experiments. The procedure is based on the graphical comparison of experimental binding data (ligand binding to one or two receptor subpopulations) with the theoretical values of ligand binding to one receptor population at four levels). The values of Kd and Bmax for high- and low-affinity receptors are derived from 4 horizontal deviations of experimental data from a theoretical data plot at these levels by their comparison with tabulated deviations. The correctness of the estimated parameters can be confirmed by the comparison of experimental data with those simulated on the basis of applying the values of Kd and Bmax found in the formula for ligand binding to two receptor subpopulations. The practical applicability of this procedure was demonstrated both on simulated and experimental data, and confirmed by the well known computer programs for evaluating receptor heterogeneity, namely "LIGAND" and "Affinity spectra".

Kinetics↗
PubMed1985

Inhibitory effects of pentacaine and some related local anaesthetics on rat hepatic adenylate cyclase.

In the present study effects of a new local anaesthetics, pentacaine (trans-2-pyrolidinocyclohexylester of 3-pentyloxyphenylcarbamic acid), and of some chemically related compounds on rat hepatic adenylate cyclase activity were studied under various experimental conditions. As compared with tetracaine, the local anaesthetics tested showed stronger inhibitory effects, regardless of the type of stimulating agents used to activate adenylate cyclase. The most potent effect was observed with pentacaine. Its inhibitory effects on glucagon, guanylylimidodiphosphate (Gpp/NH/p), sodium fluoride or forskolin stimulated activity suggest that it may directly act on the catalytic unit of adenylate cyclase. The same conclusion can be drawn based on its inhibitory effects on adenylate cyclase, regardless ATP concentrations used as the enzyme substrate, and on octylpyranoside solubilized enzyme activated by preincubation of the enzyme preparation with Gpp/NH/p. Structure-activity studies have suggested that the pentacaine molecule as a whole and none of its parts alone or its analogs are responsible for the inhibitory effect. However, the inhibitory effects of these compounds on the rat adenylate cyclase activity do not correlate with their local anaesthetic properties. The possibility of using adenylate cyclase inhibitors to decrease cyclic AMP production under pathological conditions, like in cholera, known to be due to a high adenylate cyclase activity, is discussed.

Adenylyl Cyclase Inhibitors↗
PubMed1980

Effects of dimethyl sulfoxide and other dipolar aprotic solvents on rat hepatic adenylate cyclase. Potentiating effects on glucagon and guanylylimidodiphosphate stimulation.

The actions of dimethyl sulfoxide (DMSO), acetone and two other aprotic solvents on the activity of rat hepatic adenylate cyclase were studied in order to detect their possible effects on both hormonal and nonhormonal enzyme stimulation. The glucagon- or guanylylimidodiphosphate [Gpp(NH)p]-stimulated activity was significantly increased by all DMSO concentrations (0.08--2.57 M) while the highest concentrations of this solvent decreased the enzyme activity stimulated by sodium fluoride. The effect of DMSO on adneylate cyclase activity is reversible and the stimulatory effect of this drug can be seen even on adenylate cyclase activity in the persistent active state induced by preincubation of the enzyme with Gpp(NH)p. An increase in adenylate cyclase activity stimulated by glucagon or Gpp(NH)p was also seen after the addition of other aprotic solvents (acetone, acetonitrile and dimethylformamide) to the assay system. These effects of aprotic solvents on the rat hepatic adenylate cyclase activity may be caused by an increase of membrane fluidity and facilitated movement of the adenylate cyclase subunits in the plane of the cell membrane.

Adenylyl Cyclases↗
PubMed1979

The prostaglandin antagonist polyphloretin phosphate behaves as a nonspecific inhibitor of rat hepatic adenylate cyclase.

The mechanism of the nonspecific inhibitory effects of the prostaglandin antagonist polyphloretin phosphate (PPP) was studied on a partially purified adenylate cyclase preparation from rat livers, PPP in concentrations above 100 micrograms/ml reduced the enzyme activity below basal values regardless of the stimulator used. The activity of adenylate cyclase in a persistent active state due to enzyme preincubation with guanylylimidodiphosphate (Gpp(NH)p) was inhibited 5-10 times more weakly. Kinetic studies indicate that PPP does not influence directly the catalytic site for ATP. PPP seems to produce permanent enzyme inhibition which is not antagonized by repeated washing ot the enzyme preparation. The reduced catalytic activity of adenylate cyclase retains after treatment with PPP the character of its responsiveness to the stimulators, which depends on the state of the enzyme before exposure to the inhibitor.

Adenylyl Cyclase Inhibitors↗