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Biomedical subjects

N Matsokis

Publications and source records attributed to N Matsokis.

9 recordsLinked to original sources
PubMed1995

Interaction between [3H]flunitrazepam and [3H]GABA binding in the cerebellum of reeler mice.

It has been shown that in the cerebellum of reeler mutant mice GABA levels and GABA uptake increase while GABA binding decreases. This study shows that in the cerebellum of these mutants there is also an increase of benzodiazepine receptors. This increase is observed in cerebellar homogenates, in nuclei and in membranes. The increase in the density of central (i.e. clonazepam displacable) benzodiazepine receptors is primarily reflected in binding sites located in the GABA-receptor complex. In comparison to wild-type, GABA-modulin extracted from reeler cerebellum inhibits with a greater potency [3H]GABA binding. The increase in the central-type of benzodiazepine binding and its interaction with GABA binding, observed in cerebellar membranes, is interpreted as a functional response to the decrease in GABA binding and may reflect benzodiazepine receptor condensation and/or changes of subunit composition of the GABA/benzodiazepine receptor complex. The enhanced activity of reeler GABA-modulin reflects a functional response to the increased GABA levels in reeler cerebellum. The increase of the peripheral-type (i.e. PK 11195 displacable) of benzodiazepine receptors is probably due to metabolic changes that may accompany reeler cerebellar mutation. Differences in nuclear benzodiazepine binding between reeler and wild-type mice add a physiological importance to the nuclear binding of this drug.

Animals↗
PubMed1993

Nuclear benzodiazepine binding: possible interaction with thyroid hormone receptors.

The biochemical and pharmacological properties of nuclear [3H]flunitrazepam in brain tissues were studied. Nuclear [3H]flunitrazepam binding is saturable for both central and peripheral binding sites. Inosine and hypoxanthine displace nuclear [3H]flunitrazepam binding with greater potency than the membrane [3H]flunitrazepam binding. Triiodothyronine (T3) increases the maximum number of binding sites (Bmax) of nuclear [3H]flunitrazepam binding in vitro while thyroxine (T4) does not have any effect. Diazepam reduces the affinity of nuclear 125I-T3 binding in vitro, while the Bmax is not affected significantly. Mild digestion of chromatin, using micrococcal nuclease, reveals that a major portion of nuclear [3H]flunitrazepam binding sites are located on chromatin. These data suggest a functional role for nuclear benzodiazepine binding and a possible modulatory effect of benzodiazepines on T3 binding with its nuclear receptors.

Animals↗
PubMed1989

Alteration of benzodiazepine receptors in mouse cerebellum following methylazoxymethanol treatment during development.

The specific binding of [3H]flunitrazepam was studied to biochemically specify the morphological alterations induced in mouse cerebellum by a single injection of an antimitotic agent, methylazoxymethanol (MAM) performed at the beginning of the postnatal life. The MAM injection causes a general reduction of the benzodiazepine receptors in the adult mice which is particularly severe in mice having been injected the 1st day of postnatal life (so-called MAM0 mice) as compared to animals injected the 5th day (MAM5 mice): in MAM0 mice the benzodiazepine receptor is reduced to half of the control value. The affinity of the benzodiazepine towards its receptor was not affected and the topographic and biochemical action of MAM in the central nervous system was ascertained. Correlations could be made between the biochemical modifications and the morphological alterations otherwise described.

Aging↗
PubMed1987

Absence of modification in GABA and benzodiazepine binding and in choline acetyltransferase activity in brain areas of the epileptic mutant mouse tottering.

1. In the tottering mutant mouse, which suffers from epilepsy and cerebellar ataxia, we examined whether possible changes in GABA, benzodiazepine receptors and choline acetyltransferase (ChAT) activity are implicated in the pathophysiology of these animals. 2. No alteration in GABAA and GABAB binding could be detected in cerebellar membranes of epileptic mice as compared to normal mice. 3. Benzodiazepine receptor density and affinity showed no statistical difference in cerebellar membranes of epileptic and normal mice. 4. The activity of ChAT determined in the cortices of epileptic and normal mice did not differ significantly between the two groups.

Acetylcholine↗
PubMed1986

Comparative aspects of cerebellar [3H]flunitrazepam and [3H]GABA binding.

[3H]Flu and [3H]GABA binding has been studied in mice and Rabbit cerebellum (Ce). The Bmax of [3H]Flu binding in Ce membranes is similar in all mice strains examined and Rabbit. However, in Ce homogenate there are significant differences in both kd and Bmax. Subcellular distribution shows higher [3H]Flu binding in the nuclear than in the membranous fraction. However, the [3H]GABA binding is lower in the nuclear than the membranous fraction.

Animals↗
PubMed1983

Characterization of nuclear triiodothyronine (T3) and tetraiodothyronine (T4) binding in developing brain tissue.

The main objective of this study was to characterize nuclear T3 and T4 binding in the developing rat brain. More specifically, we sought to determine (a) whether T3 and T4 bind to the same nuclear receptor, (b) whether there are multiple forms of nuclear T3 or T4 receptors, and (c) whether the above parameters are similar in nuclei of cerebral hemispheres and cerebellum of developing rat brain. From in vivo and in vitro binding experiments utilizing gel filtration techniques, we have shown that T3 binds to a main macromolecular fraction of molecular weight (M.W.) approx. 60 000 daltons; however, a minor binding component of M.W. greater than 100 000 daltons was also observed. Utilizing the same techniques it was shown that T4 does not bind with the main T3 binding macromolecule but only with the minor (M.W. greater than 100 000) binding component. Inasmuch as T4 competes with T3 for its binding, we have hypothesized that (a) the stability of the T4-receptor complex requires special stereochemical receptor-chromatin relationships that hold for in vivo or de novo conditions but not in the salt-extracted (0.4 M KCl) nuclear receptor preparation, or (b) T4 interacts with more than one receptor unit and forms unstable T4-receptor complexes corresponding to the high M.W. macromolecular fraction. The T3 and T4 binding characteristics described above were common to both brain regions at both developmental ages examined; however, these tissues were found to differ in quantitative aspects of T3 and T4 binding and with respect to the rate of the in vivo T4 to T3 conversion. We suggest that the nuclear T4 does not contribute to the end biological effects but, rather, it determines the number of free T3 binding sites. The end biological responses may thus be proportional to the binding of T3--derived from plasma and the local cellular conversion of T4 to T3--with its major nuclear binding protein and inversely proportional to the T4 nuclear concentration.

Animals↗
PubMed1978

Studies of the catalytic properties of an endonuclease isolated from Tetrahymena pyriformis.

An acid endonuclease hydrolyzing both DNA and RNA was purified from Tetrahymena pyriformis, strain E. The enzyme is distributed in all major subcellular compartments and is excreted into the growth medium towards the middle of the logarithmic phase. It hydrolyzes DNA to penta or hexanucleotides, on the average, bearing the monoesterified phosphate at the 3'-position. Particularly in early phases of the reaction it shows a very pronounced specificity for bases with a keto group at position 4 of the pyrimidine ring, such as guanine and thymine.

Base Sequence↗
PubMedDate not supplied

Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine-mediated depression.

To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CA1 area of hippocampal slices showed that PTZ-induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired-pulse stimulation paradigm showed that gamma-aminobutyric acid A (GABAA)-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CA1 area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABAA receptors (high-affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 microM on the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A1 receptor density in hippocampus (Bmax of [3H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A1-mediated adaptive mechanism that offers protection from subsequent seizures.

Action Potentials↗