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Biomedical subjects

S S Oja

Publications and source records attributed to S S Oja.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of magnesium on calcium influx activated by glutamate and its agonists in cultured cerebellar granule cells.

The effects of Mg2+ on the glutamate-, kainate-, N-methyl-D-aspartate- and quisqualate-induced influx of 45Ca2+ were studied in cultured cerebellar granule cells. The N-methyl-D-aspartate- and quisqualate-evoked influx was totally and the kainate- and glutamate-evoked influx partially blocked in 1.3 mM extracellular Mg2+. The increase in influx induced by kainate, quisqualate and glutamate was maximal at 0.1 mM Mg2+, whereas N-methyl-D-aspartate was most effective in totally Mg(2+)-free media. D-2-Amino-5-phosphonovalerate blocked partially and phencyclidine completely the enhancement of Ca2+ influx by 1 mM quisqualate in 0.1-mM Mg2+ medium. The effect of 10 microM quisqualate was also significantly inhibited by antagonists specific for different glutamate receptor subtypes, including N-methyl-D-aspartate, (RS) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and metabotropic receptors. This evidences a heterogeneous action of quisqualate, mediated by different glutamate receptor subtypes in 0.1 mM Mg2+ medium. The efficacy of quisqualate in inducing influx of Ca2+ and the selectivity of antagonists for different receptors are also modified by extracellular Mg2+.

2-Amino-5-phosphonovalerate↗
PubMed1992

Release of GABA and taurine from brain slices.

In brain slices the mechanisms of release of GABA have been extensively studied, but those of taurine markedly less. The knowledge acquired from studies on GABA is, nevertheless, still fragmentary, not to speak of that obtained from the few studies on taurine, and firm conclusions are difficult, even impossible, to draw. This is mainly due to methodological matters, such as the diversity and pitfalls of the techniques applied. Brain slices are relatively easy to prepare and they represent a preparation that may most closely reflect relations prevailing in vivo, since the tissue structure and cellular integrity are largely preserved. In our opinion the most recommendable method at present is to superfuse freely floating agitated slices in continuously oxygenated medium. Taurine is metabolically rather inert in the brain, whereas the metabolism of GABA must be taken into account in all release studies. The use of inhibitors of GABA catabolism is discouraged, however, since a block in GABA metabolism may distort relations between different releasable pools of GABA in tissue. It is not known for sure how well, and homogeneously, incubation of slices with radioactive taurine labels the releasable pools but at least in the case of GABA there may prevail differences in the behavior of labeled and endogenous GABA. It is suggested therefore that the results obtained with radioactive GABA or taurine should be frequently checked and confirmed by analyzing the release of respective endogenous compounds. The spontaneous efflux of both GABA and taurine from brain slices is very slow. The magnitude of stimulation of GABA release by homoexchange is greater than that of taurine under the same experimental conditions. However, the release of both amino acids is generally enhanced by a great number of structural analogs, the most potent being those which are simultaneously the most potent inhibitors of uptake. This may result in part from inhibition of reuptake of amino acid molecules released from slices but the findings may also signify that the efflux of GABA and taurine is at least partially mediated by the membrane carriers operating in an outward direction. It is thus advisable not to interpret that stimulation of release in the presence of uptake inhibitors solely results from the block of reuptake of exocytotically released molecules, since changes in the carrier-mediated transport are also likely to occur upon stimulation. The electrical and K+ stimulation evoke the release of both GABA and taurine. The evoked release of GABA is several-fold greater than that of taurine in slices from the adult brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Taurine release from brain slices in thioacetamide-induced hepatic encephalopathy in rats.

The possible involvement of taurine in the pathogenesis of hepatic encephalopathy was studied in rats injected with thioacetamide. Spontaneous release of exogenous labeled taurine was not affected in any brain area studied, but the potassium-stimulated release was enhanced in the striatum in thioacetamide-treated rats. High concentrations of ammonium ions also evoked greater release of taurine from striatal slices in rats with thioacetamide-induced hepatic encephalopathy.

Ammonia↗
PubMed1991

Excitatory amino acids evoke taurine release from cerebral cortex slices from adult and developing mice.

Glutamate, aspartate and the agonists of the excitatory amino acid receptors, N-methyl-D-aspartate, kainate and quisqualate, evoked more release of both endogenous and preloaded exogenous taurine from cerebral cortical slices from three-day-old than from specimens from adult mice. The N-methyl-D-aspartate- and quisqualate-evoked release was blocked by D-2-amino-5-phosphonovalerate and glutamatediethylester, respectively, in three-day-old mice but not in the adults. The kainate-evoked release was not affected by gamma-D-glutamyltaurine and gamma-D-glutamylglycine in either age group. Exposure of the slices to excitatory amino acids and their agonists caused intracellular swelling of the slices, which was directly proportional to the increase in taurine release in adult mice. In three-day-old mice the correlation between the swelling and taurine release was less pronounced. The excitatory amino acid receptors seem to modify more effectively the release of taurine in the developing than the adult brain. In the adults the evoked release of taurine may be related to cell volume regulation in the context of the excitation-coupled ionic and water movements across plasma membranes.

2-Amino-5-phosphonovalerate↗
PubMed1991

Animal models of amphetamine psychosis: neurotransmitter release from rat brain slices.

As animal models of psychosis, adult rats were exposed to different types of treatment with amphetamine: (1) subcutaneous implantation with osmotic minipumps or (2) daily intraperitoneal injections for 7 days and (3) one single amphetamine injection. Continuous administration caused tolerance, intermittent injections sensitization and the acute injection a behavioral arousal with stereotypes. All amphetamine treatments diminished the potassium-stimulated (50 mM) release of preloaded labelled dopamine from superfused striatal and frontal cortical slices in vitro. Only acute amphetamine enhanced the release of D-aspartate, an analogue of L-glutamate from frontal cortical slices. The results indicate that amphetamine profoundly affects the brain dopaminergic systems but less the glutamatergic systems. Amphetamine systematically enhanced the release of gamma-aminobutyrate (GABA) from striatal slices, but otherwise the GABAergic systems seem to be more sensitive to handling stress than to the administration of amphetamine. Besides dopaminergic mechanisms other interacting systems must thus be taken into account to explain behavioral responses to amphetamine.

Amino Acids↗
PubMed1990

Single-channel and whole-cell currents in rat cerebellar granule cells.

The patch-clamp technique was used to study both whole-cell and single-channel currents in cultured rat cerebellar granule cells. In whole-cell recordings under voltage-clamp conditions 3 types of current were found; a transient inward sodium current and a transient and a sustained outward potassium current. Single-channel currents were recorded from both inside-out and outside-out membrane patches. Three types of potassium channel were identified; two non-inactivating channels with unit conductances of 160 and 60 pS and one inactivating channel of 20 pS. No calcium currents were detected.

Action Potentials↗
PubMed1990

Modification of chloride flux across brain membranes by inhibitory amino acids in developing and adult mice.

The influx of 36Cl- was studied in membrane vesicles prepared from different brain regions from 3-day-old and adult mice. In both age groups the influx was enhanced about threefold by gamma-aminobutyric acid (GABA), which effect was blocked by bicuculline and picrotoxin but not by baclofen, characteristic of a GABAA receptor-mediated event. In samples from the adult brain stem the GABA stimulation was smaller than in samples from the other brain regions. Most of the compounds studied apparently act at the same receptor site with the following order of efficacy: muscimol greater than GABA greater than beta-alanine greater than hypotaurine greater than taurine. A number of anticonvulsant taurine derivatives were not effective and glycine only in the brain stem. The weak modulatory effects of taurine could be of significance in vivo since depolarizing stimuli release massive amounts of taurine in developing brain tissue.

Amino Acids↗
PubMed1990

Interactions of taurine with GABAB binding sites in mouse brain.

The interactions of taurine with GABAB receptors were studied in membranes from the brain of the mouse by measuring the binding of [3H]baclofen and that of [3H]GABA in the presence of isoguvacine. Taurine displaced ligand binding to GABAB receptors concentration-dependently with an IC50 in the micromolar range. The effects of baclofen on the release of taurine and GABA from slices of cerebral cortex of the mouse were assessed using a superfusion system. Potassium-stimulated release of both [3H]taurine and [3H]GABA was unaffected by baclofen but potentiated by delta-aminovalerate. The enhancement of release of [3H]taurine by delta-aminovalerate was partially antagonized by baclofen, suggesting that baclofen-sensitive receptors could modify the release.

Amino Acids↗
PubMed1990

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias.

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.

Adult↗
PubMed1990

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias.

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.

Adult↗
PubMed1990

Mechanisms of alcohol intoxication in a rodent model: blunted alcohol-opposing reaction in "alcohol-sensitive" rats.

In this paper we describe new data and review some studies on the mechanisms of alcohol-induced motor impairment in rats. Habituation to handling did not affect the naive behavioural differences between the alcohol sensitive and alcohol insensitive rat lines. Nor was there any effect on the differential sensitivities of the lines to the motor impairing and hypnotic effects of alcohol. Peripheral mechanisms may be involved in the differential behaviours of these lines, as the plasma corticosterone response was much weaker in the alcohol sensitive animals, suggesting a limited capacity to react to stress and alcohol. A similar blunted response to acute ethanol exposure was found in the uptake of the benzodiazepine antagonist [3H]Ro 15-1788 in vivo by the cerebellum of alcohol sensitive rats. The finding that these rat lines do not have any general differences in their brain inhibitory GABAergic receptors was extended to the spinal cord inhibitory glycinergic receptors, which showed only a modest line difference in their dissociation constant. The apparent localisation of the two main receptor differences (high-affinity [3H]muscimol binding and diazepam sensitivity of [3H]Ro 15-4513 binding) to the cerebellar granule layer suggests a genetic modification in the granule cells of alcohol-sensitive rats. In conclusion, our studies on acute intoxication by moderate alcohol doses show that several central nervous and peripheral factors may be involved in this behaviour. As many of these factors mitigate the effects of alcohol, alcohol antagonistic treatments should be aimed at activating and supporting multiple adaptive phenomena.

Adrenal Glands↗
PubMed1989

Displacement of excitatory amino acid receptor ligands by acidic oligopeptides.

A number of L-glutamyl and L-aspartyl dipeptides, glutathione, gamma-D-glutamylglycine and gamma-D-glutamyltaurine, were tested for their efficacy to displace ligands specific for different subtypes of excitatory amino acid receptors from rat brain synaptic membranes. In general, the L enanthiomorphs of gamma-glutamyl peptides were more potent displacers than gamma-D-glutamylglycine and -taurine but the latter were more specific for the quisqualate type of receptors. gamma-L-glutamyl-L-glutamate was the most effective dipeptide in displacing the binding of glutamate, 2-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) and 2-amino-5-phosphonoheptanoate (APH), whereas gamma-L-glutamyl-L-aspartate was the most effective in the binding of kainate. Both oxidized and reduced glutathione were inhibitory, being most potent in the binding of AMPA. gamma-L-Glutamylaminomethylsulphonate was most effective in the binding of APH. The most potent gamma-L-glutamyl peptides (glutathione, gamma-L-glutamyl-L-glutamate, -L-aspartate, and -glycine) may act as endogenous modulators of excitatory aminoacidergic neurotransmission.

Animals↗