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Biomedical subjects

R Krulík

Publications and source records attributed to R Krulík.

At least 19 recordsLinked to original sources
PubMed1995

Arginine vasopressin stimulates 32P labeling of phosphoinositides in rat pineal gland.

The peptidergic innervation of the pineal gland contains arginine vasopressin (AVP) fibers. Since the site and molecular mechanism of AVP action on the pineal signal transduction has not yet been determined, we examined whether the inositol phosphate transduction system is involved. The phosphoinositide signaling system was studied by measuring metabolic turnover of phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP) and phosphatidylinositol bisphosphate (PIP2), which reflects phosphoinositide cycle activation. AVP induced a significant increase in 32P labeling of PI, PIP and PIP2. The V1 receptor site(s) blocker for AVP abolished enhanced 32P labeling of PIP and PIP2. AVP was without effect on cAMP dependent phosphorylation. The data indicate that AVP activates the phosphoinositide signaling system via V1 receptors and is without effect on the cAMP system.

Animals↗
PubMed1995

[Ca(2+)-channel blockers and binding of tricyclic antidepressive agents].

The interactions between Ca(2+)-channel blockers (verapamil and gallopamil) and synaptic plasma membranes (SPM) from bovine brain or human lymphocyte and platelet plasma membranes were studied. Changes in binding parameters of [3H]imipramine, [3H]desmethylimipramine and [3H]gallopamil were determined after addition of unlabelled verapamil or imipramine and after addition of phosphatidylserine (PS) (PS-stimulation). Specific binding of [3H]imipramine to SPM was decreased and [3H]desmethylimipramine binding was increased by 1 microM verapamil. [3H]gallopamil binds specifically to SPM as well as to platelet and lymphocyte membranes. [3H]gallopamil binding to SPM or lymphocyte plasma membranes was PS-stimulated in contrast to platelet plasma membranes without PS effect on binding. Imipramine inhibited both [3H]gallopamil binding and PS-stimulated [3H]gallopamil binding to SPM or lymphocyte plasma membranes. Mutual effects of tricyclic antidepressants and Ca(2+)-channel blockers on their binding sites require relatively high drug concentrations. Mechanism of Ca(2+)-channel blockers action in the treatment of depression may be connected rather with changes in signal transduction through serotonin and catecholamine receptor systems than with direct interaction of drugs with binding sites for tricyclic antidepressants.

Animals↗
PubMed1993

[The effect of cocaine on binding of tricyclic antidepressives in the synaptic plasma membranes in the brain].

Effect of cocaine on binding of 3H-imipramine, 3H-desmethylimipramine, 3H-didesmethylimipramine and 3H-amitriptyline to brain synaptic plasma membranes (SPM) was studied. Binding of methylated tricyclic antidepressants was more affected. Cocaine inhibits 3H-imipramine binding at concentrations higher than 10(-5) mol/l. Binding stimulated by phosphatidylserine was affected more significantly.

Animals↗
PubMed1993

[Review of findings on binding of tricyclic antidepressants].

Authors summarize knowledge in the field of the high-affinity binding of tricyclic antidepressants on cell membranes within last 12 years. Some ideas about the significance of such binding are stated. Both the data from papers and our knowledge are discussed with regard to the possibility of their clinical application at depressed patients. Effects of the tricyclic antidepressants are linked with their influence on the active transport of neuromediators through the cell membrane but their molecular mechanisms are unknown. Present-day state of research is described and the orientation on the role of membrane phospholipids in the binding studies of the tricyclic antidepressants is emphasized.

Animals↗
PubMed1992

[Adrenergic and serotonergic receptors during depression and its therapy].

It is supposed that adrenergic and serotonergic receptor systems can play a crucial role in pathophysiology of depressive disorder. The hypothesis are based on changes of levels of serotonin and noradrenaline and on changes of their binding sites during depression and its treatment. Study of adrenergic and serotonergic receptors by pharmacological and molecular biological methods give rise to their division to many types and subtypes. This division makes possible to study the depressive disorder and its treatment on well defined receptors systems. Decreased density of beta- and 5-HT1-receptors was found during depression. Antidepressants influence 5-HT2 and adrenergic receptors mainly. Consequently, interaction between adrenergic and serotonergic systems exerts both in the origin of depression and during the treatment. Mutual influence and cooperation of different receptors systems are the main topics of research in this field.

Depressive Disorder↗
PubMed1991

Radioimmunoassay of dibenzazepines and dibenzcycloheptanodienes in body fluids and tissues.

In an attempt to establish a radioimmunoassay (RIA), imipramine and amitriptyline immunogens were prepared; desmethyl derivatives were converted into hemisuccinates, conjugated with bovine serum albumin and used for rabbit immunization. [3H]Amitriptyline (4.3 TBq/mmol) and [3H]imipramine (2.9 TBq/mmol) were prepared by catalytic dehalogenation or reductive alkylation. Dibenzazepines and dibenzcycloheptanodienes were determined in biological fluids by a direct method without deproteinization (lower detection limit of 0.5 microgram.l-1); using high-yield methods they were extracted from cell membranes. Assay of tricyclic antidepressants in humans showed that these substances disappear from plasma much earlier than from cell membranes. Dissociation of the antidepressants bound to cell membranes is slow and their plasma concentrations are not influenced by standing for 2 h at 4 degrees C. During preparing the membranes for binding studies these substances are not removed, and they may affect the results of the binding studies.

Amitriptyline↗
PubMed1991

Liposomes--model membranes to study the binding of tricyclic antidepressants.

Binding of four tricyclic antidepressants (TCAs)--imipramine, desipramine, didesmethylimipramine and amitriptyline--on the lipid part of biological membranes was studied. Heterogeneity in partitioning of these drugs in artificial lipid bilayers (liposomes) was quantified using a radioligand binding method. High-affinity binding sites on the liposomes were found and characterized by apparent dissociation constant (Kd) and by binding capacity (Bmax). Change in the membrane lipid composition affected the binding parameters of the high-affinity binding, while the ligand modification affected non-specific binding (low-affinity adsorption) of TCAs. The possible role and methodological importance of high-affinity binding to the lipid part of biological membranes are both discussed. Determination of radioligand binding on model lipid membranes is recommended to avoid certain problems in interpretation of receptor binding studies.

Antidepressive Agents, Tricyclic↗
PubMed1991

Methylated and demethylated tricyclic antidepressants and their binding to cell membranes.

We studied the binding of methylated and demethylated tricyclic antidepressants (TCA) to synaptic plasma brain membranes (SPM) and to lymphocyte, platelet and erythrocyte membranes. In the synaptic plasma membranes, more demethylated than methylated dibenzazepine derivatives were bound and the binding affinity was decreased. By contrast, in lymphocyte and platelet membranes more methylated derivatives were bound. Phosphatidylserine (PS) enhanced significantly the binding of methylated TCA in SPM without changing the dissociation constant (Kd). Lysophosphatidylserine did not affect the binding. PS also caused an increase of 3H-imipramine binding to lymphocyte membranes but the binding to platelet membranes was not affected. PS also enhanced 3H-5-HT uptake into platelets and 3H-noradrenaline uptake into lymphocytes.

Animals↗
PubMed1991

Changes of ligand binding after membrane phosphorylation.

Phosphorylation of synaptic plasma brain membranes (SPM) causes a decrease of the specific binding of demethylated tricyclic antidepressants (TCA) and changes the affinity of 3H-imipramine and 3H-desmethylimipramine binding. The decrease of TCA binding was found also in lymphocyte membranes. In platelet membranes a decreased binding was found only with demethylated dibenzazepine derivatives. Bmax and Kd values are also decreased in the presence of phosphatidic acid or alpha-glycerolphosphate.

Animals↗
PubMed1990

Plasma levels of antidepressants after their withdrawal.

The period of elimination of tricyclic antidepressant amitriptyline was studied both in plasma and erythrocytes and the influence of the preparation of blood element samples on the elimination of residual antidepressant was examined. Also the effect of stress on antidepressant level was studied. Amitriptyline was not found in plasma 14 days after its withdrawal, while at the same time its levels in erythrocytes were still well measurable. Repeated washing of erythrocyte membranes did not eliminate the residual drug completely. Demethylase activity was found to be enhanced by stress. It is suggested that all results of antidepressant binding studies may be influenced by residual drug concentration in tissues. Interindividual variability may be caused by various intensity of stress mechanisms related to depressive disorders.

Adrenal Glands↗
PubMed1989

[Biochemical requirements in tocolysis].

By a specific bond of 3H-dihydroalprenolol the number (Bmax) and characteristic (Kd) of sympathetic beta-receptors in cell membranes of the myometrium and lymphocytes of peripheral blood was assessed. The authors examined six tissue specimens taken during planned termination of pregnancy during the 38th-40th week by primary Caesarean section parallel with a peripheral blood sample. In healthy women even at the end of pregnancy the myometrium contains ample amounts of specific beta-receptors. As compared with the myometrium, the lymphocytes of the peripheral blood contain beta-adrenergic receptors of the same type as the myometrium but in much smaller amounts. So far it was not possible to show a correlation between the number of sympathetic beta-receptors in the membranes of the myometrium and of lymphocytes in the peripheral blood.

Dihydroalprenolol↗
PubMed1988

Tricyclic antidepressant binding to lymphocyte membranes and changes during depression.

The binding of [3H]imipramine, its 2- and 4-nitroderivatives and [3H]desmethylimipramine to lymphocyte membranes was determined. IC50 values for drugs and neurotransmitters to inhibit [3H]imipramine binding to lymphocyte membranes were comparable with those for brain and thrombocyte membranes. The number of [3H]imipramine and [3H]desmethylimipramine binding sites increased in depressive patients, whereas the dissociation constants remained unchanged.

Adult↗