Chloride, which comes into the forest ecosystem largely from the sea as aerosol (and has been in the past assumed to be inert), causes chlorination of soil organic matter. Studies of the chlorination showed that the content of organically bound chlorine in temperate forest soils is higher than that of chloride, and various chlorinated compounds are produced. Our study of chlorination of organic matter in the fermentation horizon of forest soil using radioisotope 36Cl and tracer techniques shows that microbial chlorination clearly prevails over abiotic, chlorination of soil organic matter being enzymatically mediated and proportional to chloride content and time. Long-term (>100 days) chlorination leads to more stable chlorinated substances contained in the organic layer of forest soil (overtime; chlorine is bound progressively more firmly in humic acids) and volatile organochlorines are formed. Penetration of chloride into microorganisms can be documented by the freezing/thawing technique. Chloride absorption in microorganisms in soil and in litter residues in the fermentation horizon complicates the analysis of 36Cl-chlorinated soil. The results show that the analytical procedure used should be tested for every soil type under study.
- MeSH
- Bacteria metabolismus MeSH
- biodegradace MeSH
- časové faktory MeSH
- chloridy analýza chemie MeSH
- halogenace * MeSH
- organické látky metabolismus MeSH
- půda analýza MeSH
- regenerace a remediace životního prostředí metody MeSH
- sterilizace MeSH
- stromy mikrobiologie MeSH
- zmrazování MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chloridy MeSH
- organické látky MeSH
- půda MeSH
Independently from its origin, trichloroacetic acid (TCA) as a phytotoxic substance affects coniferous trees. Its uptake, distribution and degradation were thus investigated in the Norway spruce/soil-system using 14C labeling. TCA is distributed in the tree mainly by the transpiration stream. As in soil, TCA seems to be degraded microbially, presumably by phyllosphere microorganisms in spruce needles. Indication of TCA biodegradation in trees is shown using both antibiotics and axenic plants.
- MeSH
- antibakteriální látky farmakologie MeSH
- Bacteria účinky léků MeSH
- biodegradace MeSH
- borovicovité metabolismus MeSH
- časové faktory MeSH
- kyselina trichloroctová farmakokinetika MeSH
- listy rostlin metabolismus MeSH
- neomycin MeSH
- půda analýza MeSH
- radioizotopy uhlíku MeSH
- rolitetracyklin MeSH
- scintilace - počítání MeSH
- streptomycin MeSH
- stromy metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- antibakteriální látky MeSH
- kyselina trichloroctová MeSH
- neomycin MeSH
- půda MeSH
- radioizotopy uhlíku MeSH
- rolitetracyklin MeSH
- streptomycin MeSH
Soils have been shown to possess a strong microbial trichloroacetic acid (TCA)-degrading activity. High TCA-degradation rate was also observed during soil extraction with water. For correct measurements of TCA levels in soil all TCA-degrading activities have to be inhibited immediately after sampling before analysis. We used rapid freezing of soil samples (optimally in liquid nitrogen) with subsequent storage and slow thawing before analysis as an efficient technique for suppressing the degradation. Frozen soil samples stored overnight at -20 degrees C and then thawed slowly exhibited very low residual TCA-degrading activity for several hours. Omitting the above procedure could lead to the confusing differences between the TCA levels previously reported in the literature.
Binding of the tricyclic antidepressant imipramine (IMI) to neutral and negatively charged lipid membranes was investigated using a radioligand binding assay combined with centrifugation or filtration. Lipid bilayers were composed of brain phosphatidylcholine (PC) and phosphatidylserine (PS). IMI binding isotherms were measured up to IMI concentration of 0.5 mmol/l. Due to electrostatic attraction, binding between the positively charged IMI and the negatively charged surfaces of PS membranes was augmented compared to binding to neutral PC membranes. After correction for electrostatic effects by means of the Gouy-Chapman theory, the binding isotherms were described both by surface partition coefficients and by binding parameters (association constants and binding capacities). It was confirmed that binding of IMI to model membranes is strongly affected by negatively charged phospholipids and that the binding is heterogeneous; in fact, weak surface adsorption and incorporation of the drug into the hydrophobic core of lipid bilayer can be seen and characterized. These results support the hypothesis suggesting that the lipid part of biological membranes plays a role in the mechanism of antidepressant action.
- MeSH
- antidepresiva tricyklická analýza chemie MeSH
- centrifugace MeSH
- chemické modely * MeSH
- filtrace MeSH
- fosfatidylcholiny analýza chemie MeSH
- fosfatidylseriny analýza chemie MeSH
- fosfolipidy analýza chemie MeSH
- imipramin chemie MeSH
- kinetika MeSH
- lipidové dvojvrstvy analýza chemie MeSH
- liposomy analýza chemie MeSH
- makromolekulární látky analýza chemie MeSH
- membrány umělé MeSH
- mozek metabolismus MeSH
- radioligandová zkouška metody MeSH
- skot MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antidepresiva tricyklická MeSH
- fosfatidylcholiny MeSH
- fosfatidylseriny MeSH
- fosfolipidy MeSH
- imipramin MeSH
- lipidové dvojvrstvy MeSH
- liposomy MeSH
- makromolekulární látky MeSH
- membrány umělé MeSH
Interspecies differences in glycosidation potential in mammalian tissues represent a factor contributing to ambiguity when endobiotic and/or xenobiotic metabolic pathways are extrapolated from animals to man. Using the TLC/autoradiographic technique, we conducted an in vitro investigation involving mouse, rat, monkey, as well as human liver and kidney microsomes to evaluate their glycoconjugation potential towards (3)H-labeled, purine-derived selective inhibitors of cyclin-dependent kinases such as olomoucine, bohemine, roscovitine, 6-(2-hydroxybenzyl)amino-2-(1-hydroxymethyl-2-methylpropyl)amino-9-isopropylpurine (compound A-4), and 6-(3-hydroxybenzyl)amino-2-[(1(R/S)-hydroxymethyl)propyl]amino-9-isopropylpurine (compound A-5) as aglycones. Principally, this study confirmed the aliphatic hydroxyl group of olomoucine-type inhibitors as a relatively suitable target for glucuronide, glucoside, xyloside, galactoside, and/or N-acetylaminoglucoside conjugation. Of the tissues examined, only the mouse microsomes were able to perform glucosidation and galactosidation reactions with the aglycones. On the other hand, monkey microsomes were superior to the mouse microsomes in a variety of glucuronide conjugates produced with compounds A-4 and A-5.
- MeSH
- chromatografie na tenké vrstvě MeSH
- cyklin-dependentní kinasy antagonisté a inhibitory MeSH
- druhová specificita MeSH
- glykosidy metabolismus MeSH
- glykosylace MeSH
- hmotnostní spektrometrie MeSH
- inhibitory enzymů chemická syntéza farmakologie MeSH
- jaterní mikrozomy metabolismus MeSH
- kinetin MeSH
- krysa rodu Rattus MeSH
- ledviny metabolismus MeSH
- lidé MeSH
- Macaca mulatta MeSH
- magnetická rezonanční spektroskopie MeSH
- mikrozomy účinky léků enzymologie MeSH
- myši MeSH
- puriny chemická syntéza farmakologie MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- cyklin-dependentní kinasy MeSH
- glykosidy MeSH
- inhibitory enzymů MeSH
- kinetin MeSH
- olomoucine MeSH Prohlížeč
- puriny MeSH
Trichloroacetic acid (TCA) as a phytotoxic substance affects health status of coniferous trees. It is known as a secondary air pollutant (formed by photooxidation of tetrachloroethene and 1,1,1-trichloroethane) and as a product of chlorination of humic substances in soil. Its break-down in soil, however, influences considerably the TCA level, i.e. the extent of TCA uptake by spruce roots. In connection with our investigations of TCA effects on Norway spruce, microbial processes in soil were studied using 14C-labeling. It was shown that TCA degradation in soil is a fast process depending on TCA concentration, soil properties, humidity and temperature. As a result, the TCA level in soil is determined by a steady state between uptake from the atmosphere, formation in soil, leaching and degradation. The process of TCA degradation in soil thus participates significantly in the chlorine cycle in forest ecosystems.
- MeSH
- biodegradace MeSH
- kyselina trichloroctová metabolismus MeSH
- půda * MeSH
- scintilace - počítání MeSH
- smrk metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyselina trichloroctová MeSH
- půda * MeSH
Synthetic cyclin-dependent kinase inhibitors have recently been referred to as effective antiproliferative agents. This study was conducted to characterize clearance of a 3H-labeled, trisubstituted purine-type inhibitor, 8-[3H]bohemine [6-benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine], in mice. Radioactivity profiles were analyzed by liquid scintillation counting and by thin layer chromatography followed by autoradiography. Metabolite structures were elucidated by mass spectrometry, NMR, and enzymatic analyses. Bohemine was rapidly and completely metabolized in vivo and disappeared from circulation during the first 60 min following intravenous administration. The metabolites were partly eliminated by the hepatobiliary tract and partly by renal excretion. The terminal hydroxyl group located at the C2 side chain of bohemine made the compound susceptible to main metabolic attacks, i.e., distinct types of conjugation reactions with glycosyl donors as well as an oxidative reaction. Other pathways were of relatively minor significance. Bohemine O-beta-D-glucoside was the most abundant metabolite to be excreted. The enzymatic mechanism responsible for bohemine glucosidation in vitro required the presence of a UDP-glucoside donor. Additional glycosidation products were observed after inclusion of UDP-glucuronide, UDP-xylose, UDP-galactose, or UDP-N-acetylglucosamine into microsomal incubates. Glycosidations occurred faster in the kidney incubates than in hepatic ones. The second principal bohemine metabolite was a carboxylic acid, 6-benzylamino-2-(2-carboxyethylamino)-9-isopropylpurine. A cytosolic, 4-methylpyrazole-sensitive alcohol dehydrogenase class I was shown to mediate oxidation of the terminal hydroxyl group of bohemine into this acid, which was the only metabolite found in the blood in significant amounts. However, it displayed only weak cyclin-dependent kinase-1-inhibitory activity (IC(50) > 100 microM) when compared with that of bohemine (IC(50) approximately 1 microM).
- MeSH
- alkoholdehydrogenasa metabolismus MeSH
- autoradiografie MeSH
- chromatografie na tenké vrstvě MeSH
- cyklin-dependentní kinasy antagonisté a inhibitory MeSH
- frakcionace buněk MeSH
- glykosidy chemie metabolismus MeSH
- hmotnostní spektrometrie MeSH
- inhibitory enzymů chemie metabolismus farmakokinetika farmakologie MeSH
- játra metabolismus MeSH
- kyseliny karboxylové krev chemie farmakologie MeSH
- ledviny metabolismus MeSH
- magnetická rezonanční spektroskopie MeSH
- mikrozomy metabolismus MeSH
- molekulární struktura MeSH
- myši MeSH
- puriny chemie metabolismus farmakokinetika farmakologie MeSH
- tritium MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkoholdehydrogenasa MeSH
- bohemine MeSH Prohlížeč
- cyklin-dependentní kinasy MeSH
- glykosidy MeSH
- inhibitory enzymů MeSH
- kyseliny karboxylové MeSH
- puriny MeSH
- tritium MeSH
Seven esters of alpha-truxillic acid have been synthesized: bis-3-piperidylpropyl ester and its quaternary bis-N-ethyl derivative, bis-N-diethylaminopropyl ester and its quaternary bis-N-methyl derivative, and bis-4-piperidylbutyl ester and its quaternary bis-N-methyl and bis-N-ethyl derivatives. All esters inhibited the specific binding of muscarinic receptor antagonist [methyl-3H]-N-methylscopolamine ([3H]-NMS) to muscarinic receptors in membranes of CHO cell lines stably expressing the human gene for the M1, M2, M3 or M4 subtype of muscarinic receptors. All esters displayed the highest potency at the M2 and the lowest potency at the M3 receptor subtype. In experiments performed on the M2 muscarinic receptor subtype, the affinity between the receptors and the esters was greatly increased when the concentration of ions was diminished. The highest affinities were found for the tertiary bis-3-piperidylpropyl and bis-4-piperidylbutyl aminoesters (equilibrium dissociation constants of 52 and 179 pM, respectively, in the low ionic strength medium). All investigated esters slowed down the dissociation of [3H]-NMS from the M2 muscarinic receptor subtype. [3H]-NMS dissociation from the M1, M3 and M4 muscarinic receptor subtypes was investigated in experiments with the bis-4-piperidylbutyl aminoester and also found to be decelerated. It is concluded that the esters of alpha-truxillic acid act as M2-selective allosteric modulators of muscarinic receptors and that, by their potency, the tertiary bis-3-piperidylpropyl and bis-4-piperidylbutyl aminoesters surpass the other known allosteric modulators of these receptors.
- MeSH
- alosterická regulace MeSH
- antagonisté muskarinových receptorů metabolismus farmakologie MeSH
- CHO buňky MeSH
- cyklobutany farmakologie MeSH
- křečci praví MeSH
- lidé MeSH
- N-methylskopolamin metabolismus MeSH
- receptory muskarinové klasifikace účinky léků MeSH
- tritium MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Názvy látek
- antagonisté muskarinových receptorů MeSH
- cyklobutany MeSH
- N-methylskopolamin MeSH
- receptory muskarinové MeSH
- tritium MeSH
- truxillic acid MeSH Prohlížeč
The relations between the concentrations of a drug in the blood (plasma, haemoglobin, red blood cells (RBCs), RBC membranes) and in the brain tissue (homogenate, membranes, cytosol) were investigated during chronic administration of imipramine. Radioimmunoassay was employed to measure the antidepressant concentrations. The concentrations were measured and analysed in 40 rats receiving various doses of imipramine. The concentration of total imipramine (imipramine + desipramine) in erythrocyte membranes (ghosts) amounted to 79.4 +/- 4.6% (mean +/- S.E.M., N = 40) of those measured in intact RBCs. Marked accumulation of the drug in the brain tissue, especially in brain cell membranes, was confirmed. The concentrations in brain tissue homogenate was found to be 14.8 times higher than that in RBCs. Values in brain membranes were 10.9 times higher than that in blood element membranes. There is a significant association between the concentrations measured in brain homogenate, the blood plasma and RBC membranes. Blood concentrations can be used to estimate imipramine concentrations in the brain.
- MeSH
- antidepresiva tricyklická aplikace a dávkování krev farmakokinetika MeSH
- cytosol metabolismus MeSH
- desipramin krev farmakokinetika MeSH
- erytrocytární membrána metabolismus MeSH
- erytrocyty metabolismus MeSH
- imipramin aplikace a dávkování krev farmakokinetika MeSH
- krysa rodu Rattus MeSH
- membrány metabolismus MeSH
- mozek metabolismus MeSH
- potkani Wistar MeSH
- radioimunoanalýza MeSH
- tkáňová distribuce MeSH
- tritium MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antidepresiva tricyklická MeSH
- desipramin MeSH
- imipramin MeSH
- tritium MeSH
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.
- MeSH
- antidepresiva tricyklická metabolismus MeSH
- blokátory kalciových kanálů farmakologie MeSH
- buněčná membrána metabolismus MeSH
- desipramin metabolismus MeSH
- fosfatidylseriny farmakologie MeSH
- galopamil farmakologie MeSH
- imipramin metabolismus MeSH
- lidé MeSH
- lymfocyty metabolismus MeSH
- skot MeSH
- synaptické membrány metabolismus MeSH
- techniky in vitro MeSH
- trombocyty metabolismus MeSH
- verapamil farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antidepresiva tricyklická MeSH
- blokátory kalciových kanálů MeSH
- desipramin MeSH
- fosfatidylseriny MeSH
- galopamil MeSH
- imipramin MeSH
- verapamil MeSH
