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Biomedical subjects

S S Oja

Publications and source records attributed to S S Oja.

At least 145 records · Page 8Linked to original sources
PubMed1989

Release of taurine and GABA from cerebellar slices from developing and adult mice.

The properties of the release of exogenous radioactive taurine and GABA from cerebellar slices from developing and adult mice were investigated using a superfusion system. Potassium stimulation (50 mM K+) caused, approximately, a 1.4-fold enhancement in the release of preloaded taurine from slices from adult mice, while the response to potassium in 7-day-old mice was about 6-fold. The potassium stimulation caused, approximately, a 3-fold increase in the release of preloaded GABA from cerebellar slices from 7-day-old mice, whereas the enhancement was about 10-fold in the adult. The actual molar amount of taurine released from the immature cerebellum was strikingly large, about 16 times larger than the amount of GABA released upon the same stimulus. Spontaneous taurine efflux was potentiated by taurine and GABA, the responses being more pronounced in the 7-day-old cerebellum, suggesting that the immature cerebellum is more prone to stimulation by homo- and heteroexchange than the mature cerebellum. Potassium-stimulated taurine release was inhibited by GABAergic substances in the adult but not in the developing cerebellum. Potassium-stimulated GABA release from the adult cerebellum was greatly increased by GABA and also moderately by muscimol and bicuculline, the effect of the latter being antagonized by taurine and hypotaurine. Taurine was thus able to modulate GABA release through bicuculline-sensitive receptors, but this modulation was not evident in cerebellar slices from 7-day-old mice. An exposure of the slices to sodium-free media greatly enhanced taurine and GABA release in both age groups. The stimulated release of GABA generally exhibited a similar calcium dependency in the adult and 7-day-old cerebella but in 7-day-old mice the stimulated release of taurine was not strictly calcium-dependent.

Aging↗
PubMed1989

Release of taurine from cultured cerebellar granule cells and astrocytes: co-release with glutamate.

The properties of the release of preloaded [3H]taurine and endogenous taurine were studied with cultured cerebellar granule cells (7-8 days in vitro) and astrocytes (14-15 days in vitro) from the rat. The spontaneous release of taurine from both cell types was slow. The release from both neurons and astrocytes was significantly enhanced by 0.1 mM veratridine, the stimulatory effect being more pronounced in granule cells than in astrocytes. No homo or heteroexchange with extracellularly added taurine or its structural analogues could be detected, suggesting that the efflux is probably not mediated via the membrane transport sites. Kainate stimulated the release more from granule cells than from astrocytes, the effect apparently being mediated by kainate-sensitive receptors. Depolarization of cell membranes by 50 mM K+ induced co-release of endogenous taurine and glutamate from both cell types. Preloaded [3H]taurine was readily released from astrocytes by potassium stimulation. Stimulated release occurred from granule cells if they had been cultured for 4 days with the label but not from the cells preloaded for only 15 min.

Animals↗
PubMed1989

Release of endogenous taurine and gamma-aminobutyric acid from brain slices from the adult and developing mouse.

The spontaneous and potassium-stimulated release of endogenous taurine and gamma-aminobutyric acid (GABA) from cerebral cortex and cerebellum slices from adult and developing mice was studied in a superfusion system. The spontaneous release of GABA was of the same magnitude in slices from adult and developing mice, but the spontaneous release of taurine was considerably greater in the adults. The potassium-stimulated release of GABA from cerebral cortex slices was about five times greater in adult than in 3-day-old mice, but the potassium-stimulated release of taurine was more than six times greater in 3-day-old than in adult mice. In cerebellar slices from 7-day-old mice, potassium stimulation also evoked a massive release of taurine, whereas the evoked release from slices from adult mice was rather negligible. Also in cerebellar slices the potassium-stimulated release of GABA exhibited the opposite quantitative pattern. The stimulated release of both GABA and taurine was partially calcium dependent. The results suggest that taurine may be an important regulator of excitability in the developing brain.

Aging↗
PubMed1988

Effect of aminooxyacetic acid on the release of preloaded [3H]GABA and radioactive metabolites from slices of developing mouse brain.

The release of [3H]gamma-aminobutyric acid (GABA) and its radioactive metabolites from slices of the cerebral cortex, cerebellum, striatum and brain stem of developing and adult mice was studied. The slices were incubated and superfused in the absence and presence of the GABA aminotransferase (GABA-T) inhibitor aminooxyacetic acid (AOAA). Exposure to 100 microM AOAA totally inhibited GABA-T and all radioactivity released from slices was in authentic GABA. In studies on developing brain the 10-microM concentration was also effective enough, except in cerebellar slices. In the absence of AOAA the major part of radioactivity spontaneously released from slices of adult cerebral cortex and cerebellum was tritiated water and still about one third part in the presence of 10 microM AOAA. Potassium stimulation induced only the release of radioactive GABA but not labeled metabolites in both presence and absence of AOAA. AOAA reduced the stimulation-induced release of GABA. It is recommended that the use of GABA-T inhibitors should be discontinued in release experiments. Then labeled GABA must be separated in the effluents from its radioactive breakdown products.

Acetates↗
PubMed1988

Modulation of GABAergic neurotransmission in the brain by dipeptides.

The effects of endogenous and synthetic peptides containing GABA or its analogues on the GABA/benzodiazepine/chloride ionophore complex. GABAB receptor, Cl fluxes, GABA release and GABA uptake were studied using synaptic membranes, crude synaptoneurosomal preparations and slices prepared from the rat and mouse brain. The sodium-independent binding of GABA was strongly inhibited by GABA-histidine, followed by gamma-glutamyl-homotaurine, GABA-glycine and gamma-glutamyl-GABA. The binding of diazepam was slightly enhanced by the same peptides. The peptides alone had no effect on the chloride fluxes, but GABA-histidine, gamma-glutamyl-GABA and GABA-glycine enhanced while gamma-glutamyl-homotaurine and GABA-taurine inhibited GABA-stimulated chloride uptake. GABA-histidine was the most effective displacer of baclofen binding, but gamma-glutamylhomotaurine was entirely ineffective. The uptake of GABA was markedly inhibited in synaptosomal preparations by GABA-histidine, while all other peptides were less effective. gamma-Glutamyl-taurine attenuated but gamma-glutamyl-homotaurine and GABA-glycine enhanced the potassium-stimulated release of GABA. The present actions of GABA-histidine in vitro may be of significance for GABAergic neurotransmission in vivo.

Animals↗
PubMed1988

Release of taurine, GABA and dopamine from rat striatal slices: mutual interactions and developmental aspects.

The spontaneous and potassium-stimulated release of preloaded taurine and GABA from striatal slices of adult and 7-day-old rats were studied using a superfusion system. Particular attention was paid to mutual interactions of taurine and GABA with dopamine in the release processes. Potassium stimulation (50 mM) enhanced taurine release more in the immature than in the adult striatum, whereas the response was the opposite with GABA release. Spontaneous taurine efflux was increased by dopamine and apomorphine, whereas stimulated release was suppressed by these agents in both age groups. This dopamine effect was partially antagonized by haloperidol, suggesting that dopaminergic systems were able to modify taurine release, possibly via dopaminergic receptors. Dopamine and apomorphine had similar but more inconsistent effects on striatal GABA release, which were not, however, mediated through conventional dopamine receptors. Stimulation with 25 mM K+ caused an 11-fold increase in striatal dopamine release: this effect was potentiated by taurine, while the actions of GABA on dopamine release were variable.

Animals↗
PubMed1988

Effects of taurine on the influx and efflux of calcium in brain slices of adult and developing mice.

45Ca2+ influx was reduced by 10-mM taurine during a 5-min incubation in slices from the cerebral cortex, cerebellum and brainstem of adult mice. In both adult and developing cerebral cortex and cerebellar slices a 30-min exposure to 1.0-mM taurine was likewise effective on resting Ca2+ influx whereas in slices depolarized by 50 mM K+ the influx was not affected. Ca2+ efflux from adult mouse cerebral cortex slices was affected by extracellular Na+ (0-180 mM) but not by K+ (50 mM) or taurine (1 mM). In cerebral cortex slices of 3-day-old mice K+ depolarization stimulated Ca2+ efflux, which effect was antagonized by 1.0 mM taurine. The results suggest that taurine is able to modify Ca2+ influx and efflux in both adult and developing brain but only at relatively high concentrations.

Animals↗
PubMed1987

Taurine and GABA release from mouse cerebral cortex slices: potassium stimulation releases more taurine than GABA from developing brain.

The release of exogenous taurine and gamma-aminobutyric acid (GABA) was studied with slices from the developing mouse cerebral cortex. The spontaneous efflux of GABA increased with the cerebral GABA content during postnatal development, while the spontaneous efflux of taurine was approximately the same in both neonate and adult mice, in spite of a several-fold higher cerebral taurine content in the former. GABA, taurine and their structural analogues caused marked homo- and hetero-trans-stimulation of the release in both adult and developing mice, probably via membrane transport sites. The release was greatly enhanced by both 0.01 mM veratridine and exposure to sodium-free medium, the effects being more pronounced with GABA in the adults and with taurine in the neonates. The excitatory amino acids homocysteate, aspartate and kainate enhanced taurine release particularly from the developing cerebral cortex but were not effective on GABA release in the adults. The potassium stimulation of taurine release had a strikingly slow time course in both adult and developing mice. The responses in GABA release were also fairly slow in the neonates. Potassium stimulation evoked a large release of GABA in adult but not in developing mice. The evoked taurine release was in developing mice several-fold greater than the evoked GABA release, decreasing in magnitude with age. The potassium-stimulated release was only partially calcium dependent, more so with GABA in the adults and with taurine in the neonates, but a high magnesium ion concentration inhibited the release of both amino acids more strongly in the latter age group. Verapamil (0.1 mM) almost abolished the potassium stimulation of GABA release in both adult and neonate mice and was more effective on taurine release in neonate mice. The results suggest that taurine, not GABA, is the major inhibitor of excitability in developing mouse brain.

Aging↗
PubMed1987

Tetanus toxin does not affect the release of noradrenaline and taurine from rat cerebral cortex slices evoked by high K+ and Na+-free media.

Noradrenaline and taurine release from superfused rat cerebral cortex slices was stimulated by potassium ions, veratrine, ouabain and omission of sodium ions. Tetanus toxin enhanced only the ouabain-evoked calcium-dependent noradrenaline release and the ouabain-evoked calcium-independent taurine release. The uptake of both was marginally affected.

Animals↗
PubMed1987

Cation effects on taurine release from brain slices: comparison to GABA.

The effects of cations on the spontaneous and potassium-stimulated taurine release from mouse cerebral cortex slices were assessed with an emphasis on the as yet unestablished calcium dependence of the stimulated release. Spontaneous and stimulated GABA release was analyzed for comparison. A depolarizing concentration (50 mM) of potassium ions caused an approximately 3.5-fold increase in taurine release and the omission of sodium a 6-fold enhancement. GABA release was increased by the same stimuli about 20- and 34-fold, respectively. Omission of calcium ions greatly enhanced basal taurine and GABA release when the medium was supplemented with the calcium chelator ethylenediaminetetraacetate. The potassium stimulation was then abolished, however, with taurine even more readily than with GABA. Magnesium and calcium ions had antagonistic effects on the stimulated release, more clearly with taurine than with GABA. Verapamil abolished the potassium stimulation of both taurine and GABA release, the latter being more sensitive. Although the stimulated taurine release was less in magnitude and had a slower time course than the GABA release, the results are not at variance with the possible neurotransmitter role of taurine.

Animals↗
PubMed1987

Taurine and GABA release from mouse cerebral cortex slices: effects of structural analogues and drugs.

The effects of structural analogues, excitatory amino acids and certain drugs on spontaneous and potassium-stimulated exogenous taurine and GABA release were investigated in mouse cerebral cortex slices using a superfusion system. Spontaneous efflux of both amino acids was rather slow but could be enhanced by their uptake inhibitors. Taurine efflux was facilitated by exogenous taurine, hypotaurine, beta-alanine and GABA, whereas GABA, nipecotic acid and homotaurine effectively enhanced GABA release. The stimulatory potency of the analogues closely corresponded to their ability to inhibit taurine and GABA uptake, respectively, indicating that these efflux processes could be mediated by the carriers operating outwards. Glutamate induced GABA release, whereas taurine efflux was potentiated by aspartate, glutamate, cysteate, homocysteate and kainate. The centrally acting drugs, including GABA agonists and antagonists, as well as the proposed taurine antagonist TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide), had no marked effects on spontaneous taurine and GABA release. Potassium ions stimulated dose-dependently both taurine and GABA release from the slices, the responses of taurine being strikingly slow but sustained. Exogenous GABA and nipecotic acid accelerated the potassium-stimulated GABA release, whereas picrotoxin and bicuculline were ineffective. The potassium-stimulated taurine release was unaltered or suppressed by exogenous taurine and analogues, differing in this respect from GABA release. The apparent magnitude of the depolarization-induced GABA release is thus influenced by the function of membrane transport sites, but the same conclusion cannot be drawn with regard to taurine. Haloperidol and imipramine were able to affect the evoked release of both taurine and GABA.

Animals↗
PubMed1987

Effects of the anticonvulsant taurine derivative, taltrimide, on membrane transport and binding of GABA and taurine in the mouse cerebrum.

The effects of a new anticonvulsive derivative of taurine, taltrimide (2-phthalimido-ethanesulphon-N-isopropylamide), and its metabolites on the release, uptake and binding of gamma-aminobutyric acid (GABA) and taurine, were studied in the cerebrum of the mouse. The potassium-stimulated release of taurine from slices of cerebral cortex was inhibited in vitro by taltrimide and its dealkylated metabolite, whereas the stimulated release of GABA was significantly enhanced by both drugs. The uptake of taurine and GABA were not markedly affected. Both taltrimide and its dealkylated metabolite strongly inhibited the sodium-independent binding of taurine to synaptic membranes of brain, the effects on the binding of GABA being less pronounced. The actions on synaptic binding of taurine and on depolarization-stimulated release of GABA may be of significance for their anticonvulsant properties.

Animals↗
PubMed1987

Co-operativity in sodium-independent taurine binding to brain membranes in the mouse.

Sodium-independent taurine binding to mouse brain membranes treated twice with Triton X-100 exhibited properties of positive co-operativity, suggesting that two or more taurine molecules interact at the binding site. The proposed taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide and the new anticonvulsant taurine derivative taltrimide as well as glycine and GABA with their antagonists displaced taurine binding, strychnine being the most effective.

Animals↗
PubMed1987

Glycinergic systems in the brain stem of developing and adult mice: effects of taurine.

The release of glycine from slices of the brain stem and binding of strychnine to brain stem membranes were characterized in adult and developing mice. Spontaneous glycine efflux was markedly facilitated by homoexchange with exogenous glycine and moderately by heteroexchange with taurine. Potassium stimulation released more glycine from brain stem slices from adult than from 7-day-old mice. Potassium-stimulated glycine release was also potentiated by glycine and by the novel anticonvulsant taurine derivatives. One population of strychnine-binding sites was found in both mature and immature brain stem. The number of binding sites increased with age, whereas the affinity of the sites for strychnine remained the same. The glycine inhibition was stronger in adult than in developing mice. In the presence of taurine the affinity for strychnine decreased without any change in the maximal binding capacity, suggesting a competitive type of inhibition. The binding constant and maximal binding capacity of strychnine increased in the presence of NaCl (200 mM) both in adult and 7-day-old mice. The calculated IC50 values for displacement of strychnine binding by glycine, taurine and beta-alanine were higher in the presence than in the absence of sodium. The results show that the evoked release of glycine and the number of binding sites of strychnine increase during postnatal development in the mouse but that their characteristics do not change.

Aging↗
PubMed1987

Biochemical and clinical studies on epileptic patients during two phase I trials with the novel anticonvulsant taltrimide.

Taltrimide (2-phthalimidoethanesulphon-N-isopropylamide), a lipophilic derivative of taurine and a potent anticonvulsant in animal studies, was administered in daily doses of 1 and 2 g for 2 weeks with an interval of 2.5 months in 2 phase I clinical trials to 9 drug-resistant epileptic patients. Seizures and EEG were recorded, and routine laboratory studies conducted. Concentrations of antiepileptic drugs in plasma, of amino acids in urine and plasma, and contents of amino acids, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and cyclic nucleotides in the cerebrospinal fluid were determined. Although no clinical or neurophysiological effects were observed, an increase in the cerebrospinal fluid contents of HVA and cyclic nucleotides and changes in the concentrations of antiepileptic drugs and amino acids were found. The concentrations of HVA correlated with those of 5-HIAA and also with those of the main active metabolite of taltrimide. Biochemical changes due to taltrimide treatment resembled only partly those found after taurine treatment.

Adult↗