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J Myslivecek

Publications and source records attributed to J Myslivecek.

At least 19 recordsLinked to original sources
PubMed2007

Retinoic acid attenuates the mild hyperoxic lung injury in newborn mice.

Neonatal exposure to hyperoxia alters lung development in mice. We tested if retinoic acid (RA) treatment is capable to affect lung development after hyperoxic injury and to maintain structural integrity of lung. The gene of vascular endothelial growth factor A (VEGF-A) is one of the RA-responsive genes. Newborn BALB/c mice were exposed to room air, 40% or 80% hyperoxia for 7 days. One half of animals in each group received 500 mg/kg retinoic acid from day 3 to day 7 of the experiment. At the end of experiment we assessed body weight (BW), lung wet weight (LW), the wet-to-dry lung weight ratio (W/D) and the expression of mRNA for VEGF-A and G3PDH genes. On day 7 the hyperoxia-exposed sham-treated mice (group 80) weighed 20% less than the room air-exposed group, whereas the 80% hyperoxic group treated with RA weighed only 13% less than the normoxic group. W/D values in 80 and 80A groups did not differ, although they both differed from the control group and from 40 groups. There was a significant difference between 40 and 40A groups, but the control group was different from 40 group but not from 40A groups. The 80 and 80A groups had mRNA VEGF-A expression lowered to 64% and 41% of the control group. RA treatment of normoxic and mild hyperoxic groups increased mRNA VEGF-A expression by about 50%. We conclude that the retinoic acid treatment of newborn BALB/c mice exposed for 7 days to 80% hyperoxia reduced the growth retardation in the 80 % hyperoxic group, reduced the W/D ratio in the 40% but not in the 80 % hyperoxic group. Higher VEGF-A mRNA expression in the 80% hyperoxic group treated with RA was not significant compared to the 80% hyperoxic group.

Analysis of Variance↗
PubMed2006

The effects of stress on muscarinic receptors. Heterologous receptor regulation: yes or no?

1 Stress is usually comprehended as an event affecting mainly the catecholaminergic system, the hypothalamo-pituitary-adrenocortical (HPA) axis and the receptor systems connected to these neurotransmitters/hormones. Other neurotransmitter/hormone systems can be affected too. Here we review the available data on the effects of different stressful stimuli (physical, chemical, psychological/social, cardiovascular, affecting multiple system) on muscarinic receptors (MR). 2 The data suppose the existence of specific mechanisms that regulate the signalization through MR during different type of stress. 3 Physical stressors (cold vs. heat) reveal opposite type of changes on peripheral-tissue MRs. Chemical stressors (oxidative stress) are tightly connected with MR and it is especially interesting that the sensitivity of MR to oxidative stress is subtype-specific. It is also suggested that heterologous regulation can occur with psychological/social stressors on the organism. Cardiovascular system-disturbing stressors cause imbalance between autonomic receptors or down-regulate MR in the peripheral tissue. Immobilization caused opposite effects on MR in the central nervous system and periphery, where the changes are supposed to be due to heterologous regulation between receptor systems. 4 In conclusion, some data indicate that in specific conditions MR are regulated as a consequence of other changes rather than as a primary effect of stress. On the contrary, in some situations, MR are the first targets to respond to the stress. 5 These findings on stress-induced activity of the cholinergic system and changes in muscarinic receptors support the view that stress is a specific response of the organism.

Animals↗
PubMed2006

Development of autonomic receptors and their function in the chick heart and influence of continuous infusion of carbachol.

The development of heart rate and of muscarinic and beta-adrenergic receptors in chick heart ventricles in the last third of in ovo ontogenesis has been studied. The development of these two types of autonomic receptors does not proceed in parallel. While muscarinic receptors are stable between days 13 and 17, beta-adrenergic receptors significantly decrease in this period. Muscarinic receptors increase their number from the 17th day, and the highest density can be seen after hatching. beta-adrenergic receptors, on the contrary, do not change their density between days 17 and 19, but similarly to muscarinic receptors they increase after hatching (the density after hatching is approximately the same as on the day 13 of embryonic development). We have shown previously that stimulation of one receptor type in the system of autonomic receptors in the heart changes not only the appropriate type of receptor but also the density of the other one. We therefore wondered the information about this in the organism in development. Here we show that when we have infused the eggs in developmental period mentioned above there was no cross-regulation and that muscarinic receptors do not down-regulate. Up-regulation of muscarinic receptors was maintained when the eggs were infused by carbachol from the 13th to 14th day of in ovo development. This muscarinic receptor up-regulation was accompanied with paradoxical increase in heart rate. These events are not proteinkinase (PKC) dependent, as bisindolylmaleimide (PKC inhibitor) do not prevent these changes.

Animals↗
PubMed2006

Developmental changes of some G-protein coupled receptors affected by c-fos knock-out.

The role of c-fos gene disruption on binding characteristics of selected G protein-coupled receptors has been investigated. The following receptors were studied: muscarinic receptors (MR), alpha1-adrenoceptors (AAR), beta-adrenoceptors (BAR), D1-like dopamine receptors (D1R), D2-like dopamine receptors (D2R). We have tested the hypothesis that c-fos gene disruption would not influence the receptor density in central nervous system (CNS: brain cortex and cerebellum) and in the periphery (lung, heart). We found that both in the periphery and in the CNS there were important changes in receptor density. Both MR and BAR were increased in the lung and heart. The effects of c-fos gene disruption in CNS were more selective. In general, the receptors that activate Gq-phospholipase C-proteinkinase C pathway (AAR, MR) were affected, while the others (that activate/or inhibit adenylyl cyclase: BAR, D1R, D2R) were not. These results show that disruption of c-fos gene could significantly change the expression of G protein-coupled receptors. Moreover, these changes could be comprehended as one of the adaptive mechanisms that help the organism to cope with c-fos gene disruption.

Animals↗
PubMed2005

Identification of all alpha1-adrenoceptor subtypes in rat lung.

The function of lung tissue is regulated via a release of neurotransmitters from autonomic nerves. The neurotransmitters of sympathetic nervous system, adrenaline and noradrenaline, activate both alpha-adrenoceptors and beta-adrenoceptors. Although the function and expression of beta-adrenoceptors can be considered major, some doubts exist about the function and expression of alpha1-adrenoceptor subtypes in the lung tissue. Therefore a set of competition binding experiments was employed in order to discriminate between the alpha1-adrenoceptor binding site subtypes in the rat lung. We identified three subpopulations of alpha1-adrenoceptor binding sites in the rat lung (alpha1A, alpha1B and alpha1D).

Animals↗
PubMed2003

[Regulation of G-protein-coupled receptors].

G protein coupled receptors are the largest family of receptors in the organism. When the transmitter input is significantly changed in comparison to normal condition, the homologous or heterologous regulation can occur. Homologous regulation represents the situation in which the properties of the receptor system just influenced via extracellular signalling are changed. Heterologous regulation can manifest despite that the extracellular signalling influence the receptors. It is possible to comprehend such changes as one of the level of homeostasis. Both homologous and heterologous regulations play a role in physiological and pathophysiological processes. In the basic scheme this regulations are comprehend as phosphorylation-based events. We discuss other possible pathways of receptor regulation in this review.

GTP-Binding Protein Regulators↗
PubMed2003

Regulation of adrenoceptors and muscarinic receptors in the heart.

Receptor activation results in homologous regulation and can also affect other types of receptors (a process that has been reported to heterologous regulation). Heart cells express subtypes of muscarinic receptors and adrenoceptors, almost antagonistic in their action (M2 muscarinic receptors and beta1-adrenoceptors). Therefore, they provide an excellent model of heterologous regulation. Moreover, the minor subtypes of adrenoceptors and muscarinic receptors have been identified in the heart cells. The physiological significance of the minor subtypes is now under keen investigation and their function can be considered as complementary to the major subtypes. Taken together, it seems that the minor subtypes may play an important role in the receptor-heart function homeostasis and that heterologous regulation seems to exist in many heart receptor types and in the above mentioned pair of receptors.

Animals↗
PubMed2003

[Regulation of receptor functions in the CNS].

The basic condition of life is capability to adapt not only to external but also to internal milieu conditions. I.e. receptors are able to change the intensity of signal transduction from the extracellular to the intracellular compartment in a short period. In a specific manner it concerns all receptor structures, both if they are located in cytoplasm or within the membrane. This review concentrates to the mechanisms existing in G protein-coupled receptors. Those protein structures can undergo a homologous or heterologous regulation. Homologous regulation means that only the properties of a receptor system influenced via extracellular signalling are changed. Heterologous regulation means, that receptor properties are changed despite that the extracellular signalling did not influence the receptor. It is possible to consider such changes as one of the level o homeostasis. Both homologous and heterologous regulations are essential for many physiological and pathophysiological processes. The most important examples of these processes, especially in the central nervous system, are reviewed here.

Animals↗
PubMed2001

[Current views on receptors for mediators of the autonomic nervous system of the heart].

Heart function reflects activity of the heart pacemaker cells. This basic function is permanently influenced by two practically antagonistic systems--sympathetic and parasympathetic systems. They control not only the force of contraction (influencing calcium channels), heart rate (via potassium channels), but also arterioventricular transduction (changing the threshold for ion channels opening by influencing the maximal negative level of the membrane potential). Last few years changed our view on autonomic receptor expression in the heart. It is assumed that the heart adrenoreceptors are represented by alpha 1, beta, and beta 2 subtypes. The expression of beta 3 subtype is still controversial, similarly the existence of other, fourth beta-adrenoreceptor subtype, putative beta 4, is uncertain. Moreover, the end of the twentieth century brought the correction of former idea about a single muscarinic receptor subtype (M2) in the heart. Functional correlates of these findings are also reviewed.

Animals↗
PubMed2001

Muscarinic receptor subtypes in the heart--how many and why?

Muscarinic receptors are coupled to G proteins and to date, five subtypes have been characterized. These subtypes differ in their effects on second messenger production. Odd-numbered subtypes activate phospholipase C beta, and then they increase the production of inositoltrisphosphate and diacylglycerol. Even-numbered subtypes inhibit adenylylcyclase. The expression of individual subtypes is quite tissue specific. The heart tissue is realized as M2 predominant organ (in mammals; the muscarinic population in birds consist of M2 and M4 receptors). This article focuses on the possibility of existence of further muscarinic receptor subtypes in avian and mammalian heart in consequences with activation of phosphoinositid metabolism in the heart.

Animals↗
PubMed2000

Mechanisms of G-protein coupled receptor regulation.

It has been realized recently that the enhanced or lowered activation of a certain receptor type brings about changes not only in the sensitivity (or density) of this particular receptor type in cell membranes by producing its desensitization or sensitization, down- or up-regulation (i.e. homologous regulation), but also it could change the function (or density) of other receptors (cross-regulation). This review is focused on mechanisms of the homologous regulation (changes in the pathway activated by the appropriate type of receptor) and possible mechanisms of cross-regulation (changes in pathway activated by other type of receptor).

Down-Regulation↗
PubMed1999

Nitric oxide synthase (NADPH-diaphorase) content in brain neurons of neonatal rats after inhibitory learning and intervention into nitric oxide metabolism.

Four-day-old rat pups were taught to avoid an electrified grid under the influence of increased nitric oxide availability in brain (by a nitric oxide substrate L-arginine) that alleviated learning or decreased nitric oxide (due to the action of a blocker of nitric oxide synthase nitro-L-arginine) that impaired learning. Three hours after criteria meeting, the pups were killed for analysis of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase content in brain cells and neuropil. In the cingulate gyrus, NADPH-diaphorase-positive staining was increased after L-arginine, but an opposite picture was observed in hippocampus and basal ganglia, i.e. an increase after the blocker nitro-L-arginine. A noteworthy accumulation of NADPH-diaphorase in hippocampal cells might be tentatively explained by the blocking effect of nitro-L-arginine not allowing NADPH-diaphorase to leave the cells. Application of L-arginine or nitro-L-arginine provoked only minor changes in the studied structures of non-learned pups with the exception of hippocampus where nitro-L-arginine increased the width of neuropil, but to a lesser degree than in learned animals. These results clearly show that both manipulations, i.e. drug application and learning, only have a significant effect on the changes in NADPH-diaphorase positivity in brain neurons.

Animals↗
PubMed1998

Heterologous regulation of muscarinic and beta-adrenergic receptors in rat cardiomyocytes in culture.

Previous work indicated that hyperstimulation of muscarinic receptors brings about profound changes not only in the density of the muscarinic receptors, but also of the beta-adrenoceptors in rat heart atria in vivo. We have now investigated whether a similar receptor cross-regulation occurs in cardiomyocytes in vitro. Cardiomyocytes from 3-4 day old rats were exposed to chemical agents on days 5-6 in culture. Densities of muscarinic and beta-adrenergic receptors were measured according to the binding of N-[3H]methylscopolamine and [ H]CGP 12177, respectively, to cell surface membranes and cell homogenates. Exposure of cells to the muscarinic agonist carbachol (1 mmol/l) brought about a profound decrease in the number of muscarinic receptors. The number of beta-adrenoceptors displayed biphasic changes, being augmented after 24 h (by 20-45% on the cell surface and by 29% in the homogenate) and diminished after 48 h and 72 h (after 48 h, decrease by 44-75% on the cell surface and by 36% in the homogenate). These effects of carbachol were not prevented by dimethylaminopropyl-bis-indolylmaleimide, the inhibitor of protein kinase C. Exposure of cells to the beta-adrenoceptor agonist isoprenaline (0.1 mmol/l) strongly diminished the number of beta-adrenoceptors on the cell surface and in the homogenate. The density of muscarinic receptors on the cell surface was diminished by 24-43% after 24 h exposure to isoprenaline and unchanged after 48 h, whereas the concentration of muscarinic receptors in the homogenate was unchanged after 24 h and increased by 20% after 48 h. The isoprenaline-induced decrease in the density of cell surface muscarinic receptors could not be simulated by forskolin and was not abolished by the protein kinase A inhibitors Rp-cAMPS and HA-1004. Dibutyryl cyclic AMP diminished the density of cell surface muscarinic receptors more than that of the beta-adrenergic receptors. Our data reveal a novel phenomenon of a biphasic change (an increase followed by a loss) in the density of beta-adrenoceptors during exposure of cardiocytes to carbachol. Activation of beta-adrenoceptors brings about less conspicuous changes in the density of muscarinic receptors. The observed phenomena of receptor cross-regulation cannot be explained by simple activations of protein kinases A and C.

Adrenergic beta-Agonists↗
PubMed1998

[Morphologic and functional characteristics of an animal model of cerebellar degeneration (lurcher mutant mice)].

Lurcher mutant mice are characterized by genetically determined degeneration of cerebellar Purkinje cells, granule cells and inferior olivary neurons (ION). In the morphological part of this study Lurcher mutant and wild type mice were given intraperitoneal injections of 3-acetylpyridine (3AP) to look at the effect of this neurotoxin and niacinamide antagonist on the ION. Intraperitoneal administration of 3AP is characterized by the different sensitivity of ION in Lurcher mutant mice and wild type mice in both infant and young adult animals. Lurcher mutants suffered a destruction of these neurons while wild type mice were unaffected. Since the cerebellum plays an essential role in the sphere of motor learning and behavior, in the functional part of this study we investigated some characteristics of early learning in Lurcher mutant and wild type mice. The first experimental results show some differences in the inhibitory reaction of the passive avoidance between Lurcher mutant and wild type mice in early ontogeny, during the first month of their life. Both morphological and functional findings show not only different effects of 3AP on genetically mutated and wild type mice in the same inbred strain but also some functional changes in the sphere of early learning and memory as well.

Animals↗
PubMed1998

[Cross-regulation between muscarine and beta-adrenergic receptors].

Muscarinic and beta-adrenergic receptors belongs to the family of G protein coupled receptors. Their activation brings about nearly antagonistic effects in most tissues. We demonstrate on the model of myocardial cells, that their regulation is mutually interconnected and that the cross-regulation could represent new level of homeostasis maintenance.

Animals↗
PubMed1997

Inhibitory learning and memory in newborn rats.

Firstly, the noetic value of the ontogenetic approach to the problems of learning and memory is emphasized; then the heterochrony and uneven time course of the development of neural systems are accentuated, which fully holds for the basic cognitive functions. Contrary to a broadly accepted opinion, that inhibitory learning develops later in the ontogeny, using a special method of passive avoidance (with gentle air flow inciting the new-born animal to move), the ability of new-born rats to learn an inhibitory reaction even several hours after delivery and remember it for 24 hr has been proven; special control experiments have excluded any possibility that it is a non-specific reaction. To get it, the specific features of the neonatal organism are to be considered and its functional capabilities not to be overlooked. This conditioned reaction as well as its 24 hr memory develops with a temporary reversal during several postnatal days, needing decreasing numbers of trials to meet the criteria. In the analysis of their mechanisms, it has been shown that adequate functioning of peripheral receptor zones providing afferent inputs from somatosensory areas of the conditioned stimulus is considerably involved in their establishment. Increased dendritic branching has been found in hippocampus and Meynert nucleus the following day after learning in the neonatal period. Special attention is devoted to the involvement of transmitters and/or modulators; the action of acetylcholine, noradrenaline, dopamine and nitric oxide has been discovered during the first postnatal hours; their application after meeting criteria displays a time and age dependent effect with a general characteristic of memory improvement. Neonatal learning under nitric oxide influence changes nitric oxide-synthase content in the brain. Increasing dopamine and nitric oxide availability in the brain improves both learning and memory, and their joint application positively alleviates these phenomena further. Dopamine and its D1 receptor agonists counterbalance decreased nitric oxide after nitric oxide synthase blockade; increased nitric oxide in brain and dopamine receptor antagonists similarly counterbalance each other.

Animals↗
PubMed1997

Interactions between nitric oxide and dopamine in inhibitory learning and memory in newborn rats.

Taking into account our previous results on dopamine and nitric oxide effects on neonatal inhibitory learning and memory in rats, the mutual interactions of the two molecules were studied in this experimental paradigm. Both increased dopamine content and nitric oxide bioavailability in the brain after application of dopamine and L-arginine as substrate for nitric oxide synthase solutions into lateral cerebral ventricles improved learning and 24 h memory. Joint application of dopamine and L-arginine yielded still more improvement. Learning and memory processing were dose dependently enhanced by D1 receptor agonists as well, whereas D1 receptor antagonists had an opposite and also dose-dependent effect. Dopamine or D1 receptor agonists administered together with nitro-L-arginine, a nitric oxide synthase inhibitor that impaired learning and memory due to a decreased nitric oxide availability, antagonized the effect of nitro-L-arginine, as did L-arginine. D1 receptor antagonists impaired both learning and memory, and L-arginine rendered learning values normal. The dopamine and D1 receptor-agonist effect on 24 h memory was concentration dependent, and their higher concentrations substantially increased the retention indexes. The intimate mechanisms of these interactions are to be identified in further experiments.

Animals↗