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S S Oja

Publications and source records attributed to S S Oja.

At least 109 records · Page 6Linked to original sources
PubMed1994

Release of [3H]GABA evoked by glutamate agonists from hippocampal slices: effects of dithiothreitol and glutathione.

The effects of dithiothreitol (DTT) and, reduced (GSH) and oxidized (GSSG), glutathione on the release of [3H]GABA evoked by glutamate and its agonists were studied in rat hippocampal slices. DTT had no effect on the basal release of [3H]GABA but it enhanced and prolonged the glutamate agonist-evoked release. This effect was abolished by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801), a noncompetitive NMDA antagonist, and blocked by Mg2+ ions. It was only slightly attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, and not affected by L-(+)-2-amino-3-phosphonopropionate (L-AP3), a selective antagonist of the metabotropic glutamate receptor. The effect of DTT on the NMDA-evoked release of GABA was only slightly affected by extracellular Ca2+ but completely blocked by verapamil even in the absence of Ca2+. GSH and GSSG attenuated or abolished the effects of DTT on the agonist-induced release of [3H]GABA. The results imply that the enhanced and prolonged release of GABA evoked by the coexistence of DTT and excitatory amino acids and attenuated by endogenous GSH and GSSG is a consequence of sustained activation of the NMDA receptor-governed ionophores, which contain functional thiol groups. DTT, GSH and GSSG may regulate the redox state and accessibility of these groups. In addition to the influx of extracellular Ca2+, DTT mobilizes Ca2+ from intracellular pools distinct from those regulated by metabotropic glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Long-term treatment with ammonia affects the content and release of taurine in cultured cerebellar astrocytes and granule neurons.

High (50 mM) K+ stimulated the release of preloaded [3H]taurine from cultured cerebellar astrocytes and granule neurons with a delayed onset and only when the stimulus was applied in isoosmotic, but not in hypertonic (50 mM sucrose) medium. The process thus exhibited characteristics typical for the osmosensory or osmoregulatory response noted in a variety of nerve cell cultures. Addition of 1 mM NH4Cl to the astrocytic culture for 24 h increased the unstimulated release of [3H]taurine. However, this increase was not suppressed in a hypertonic medium, thus differing from the response accompanying regulatory volume decrease in astrocytes exposed to hypoosmolar or high potassium media. In accordance with the enhanced unstimulated release of [3H]taurine, addition of 1 mM NH4Cl decreased by 15% the taurine content in these cells. However, the addition abolished the stimulatory effect of 50 mM K+ on [3H]taurine release, indicating a loss of the osmosensory response of the cells. By contrast, treatment of granule neurons with 1 mM NH4Cl for 24 h remained without effect on any of the components of [3H]taurine release. However, the treatment increased the taurine content in granule neurons by 43%. This increase resembles the response usually noted in astrocytes adapted to hyperosmotic medium and may at least in part, reflect adaptation of the neurons to the slight increase in medium osmolarity due to the addition of ammonium chloride. The results are consistent with the selective vulnerability of astrocytes to hyperammonemic conditions, adding credence to earlier morphological observations.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed1994

Regulation of D-aspartate release by glutamate and GABA receptors in cerebral cortical slices from developing and ageing mice.

The basal release of D-[3H]aspartate, an unmetabolized analogue of glutamate, from cerebral cortical slices remained at the same level from three-day-old to 24-month-old mice, but the response to K+ stimulation (50 mM) was smaller in young than in adult or aged mice. Kainate, N-methyl-D-aspartate and quisqualate (0.1 mM) stimulated the basal release of D-aspartate in the cerebral cortex of seven-day-old mice, the effects of kainate and N-methyl-D-aspartate being reduced by their antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine maleate, respectively, indicating that in the immature cerebral cortex the kainate and N-methyl-D-aspartate types of the glutamate receptor are involved in the basal release. The K(+)-stimulated release was not affected by glutamate agonists in developing mice, though they markedly attenuated the evoked release in adults. The inhibitory amino acids GABA, taurine and glycine depressed the K(+)-stimulated release only in the adult cerebral cortex. The action of GABA was abolished by bicuculline, demonstrating the involvement of presynaptic GABAA receptors. The glycine effect was strychnine-insensitive, characteristic of the glycine modulatory site in the N-methyl-D-aspartate receptor. This kind of regulation by both kainate and N-methyl-D-aspartate receptors could be of physiological significance, particularly in the immature cerebral cortex.

Aging↗
PubMed1994

Characterization of sodium-independent beta-alanine binding to cerebral cortical membranes from 7-day-old and adult mice.

The sodium-independent binding of beta-alanine to cerebral cortical membranes from adult (3- and 12-month-old) and developing (7-day-old) mice was characterized for the first time. The binding was saturable in each age group, consisting of only one component. The affinity for beta-alanine was highest and the number of available binding sites greatest in young animals. The binding was not affected by strychnine, but inhibited by beta-alanine itself, glycine, L-alanine and L-serine, the IC50 values being lower in immature mice. Glycine was shown to be a competitive inhibitor. The binding was also inhibited, albeit only in adults, by N-methyl-D-aspartate receptor antagonists acting at the glycine modulatory site and by some GABAergic substances. It is concluded that even though beta-alanine may possess binding sites of its own, particularly in the immature cerebral cortex, beta-alanine could at least partly bind to strychnine-insensitive glycine sites in the N-methyl-D-aspartate receptor complex.

Animals↗
PubMed1993

Loss of GABAB binding sites in the cerebral cortex of rats with acute hepatic encephalopathy.

The binding of [3H]GABA to GABAA and GABAB binding sites was measured in cerebral cortical membranes derived from control rats and rats with acute hepatic encephalopathy (HE) induced with a hepatotoxin, thioacetamide. HE did not affect the kinetic parameters (KD and Bmax) for the GABAA binding site. However, HE decreased Bmax (but not KD) for the GABAB binding site to 32% of the control level, indicating a substantial loss of GABAB receptors. Since GABAB receptors control the cerebral cortical release of the amino acid neurotransmitters glutamate and GABA, the loss of GABAB receptors is likely to contribute to the array of disturbances of glutamatergic and GABAergic neurotransmission known to accompany HE.

Acute Disease↗
PubMed1993

Glutathione modulates the N-methyl-D-aspartate receptor-activated calcium influx into cultured rat cerebellar granule cells.

The effects of reduced (GSH) and oxidized (GSSG) glutathione and dithiothreitol (DTT) and L-cysteine on the influx of 45Ca2+ were studied with cultured cerebellar granule cells. DTT slightly enhanced the basal influx but strongly activated the influx stimulated by glutamate or N-methyl-D-aspartate (NMDA). The effects on the kainate- or quisqualate-induced influx were less pronounced. Extracellular GSH had no effect on the basal influx of Ca2+. A concentration of 0.5 mM GSH slightly activated the glutamate- and NMDA-induced influx while GSSG was inhibitory. The enhancement by DTT and cysteine of the responses to excitatory amino acids was attenuated by GSH and GSSG. We propose that both the accessibility and redox state of the functional sulfhydryl groups in NMDA receptor-ionophores may be regulated by endogenous glutathione. These effects are attributed to the gamma-glutamyl moiety and sulfhydryl group in the tripeptide molecule.

Animals↗
PubMed1993

Phencyclidine treatment in mice: effects on phencyclidine binding sites and glutamate uptake in cerebral cortex preparations.

The effects of a psychotomimetic drug, phencyclidine (PCP), on glutamatergic neurotransmission were studied in mice. The binding of tritiated N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to cerebral cortical membranes and the uptake of [3H]glutamate by cortical synaptosomal preparations were assessed after PCP treatment (1 mg/d/mouse for 3 days) with implanted minipumps. The binding capacity Bmax of TCP significantly increased but the binding constant KD remained the same after PCP exposure, indicating that more binding sites became available. The basic properties of the binding remained unaltered but the actions of glutamate, glutamate receptor agonists and glycine were potentiated in PCP-treated mice. The uptake of glutamate was saturable, consisting of both high- and low-affinity transport components. After PCP exposure the transport constant Km of the high-affinity component increased and that of the low-affinity component was not changed. The maximal velocity V of the high-affinity component increased while that of the low-affinity transport decreased. Moreover, inhibition by structural analogues was potentiated, suggesting modification of the glutamate transporter. The results show that chronic PCP treatment, used as a model of psychosis, markedly affects the studied glutamatergic parameters.

Animals↗
PubMed1993

Strychnine-insensitive glycine binding to cerebral cortical membranes in developing and ageing mice.

The strychnine-insensitive binding of [3H]glycine was characterized in purified cerebral cortical membranes from mice aged from 7 days to 22 months. The binding was saturable, exhibiting only one component during the whole life-span studied. The binding constant KD did not change during development and ageing, whereas the maximal binding capacity Bmax, calculated per protein content, increased up to the age of two weeks and then again in ageing animals (18- and 22-month-olds). The binding was similarly inhibited by the antagonists 7-chlorokynurenate, 3-amino-1-hydroxypyrrolidin-2-one (HA-966) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in 7-day-, 3-month- and 12-month-old mice. The inhibition caused by glycine, L-serine and beta-alanine also remained unaltered during the whole life-span. beta-Alanine was a noncompetitive inhibitor. The alterations in the maximal binding capacities during development and ageing could be of importance in the regulation of NMDA receptors, which have been implicated in synaptic potentiation, developmental processes and various pathological conditions.

Aging↗
PubMed1993

Phencyclidine-binding sites in mouse cerebral cortex during development and ageing: effects of inhibitory amino acids.

The binding of N-[1-(2-thienyl)cyclohexyl]-[3H]piperidine ([3H]TCP) to the phencyclidine-binding sites in the N-methyl-D-aspartate (NMDA) receptor complex-associated ion channel was characterized in cerebral cortical membranes from 3-day-old to 24-month-old mice. The binding was saturable, exhibiting only one binding component during the whole life-span studied. The maximal binding capacity Bmax, calculated per protein content, decreased during postnatal development until 3 months of age, remaining thereafter constant in ageing mice, thus indicating the greatest availability of phencyclidine-binding sites in the immature cerebral cortex. The binding constant KD increased during the first postnatal week, remained thereafter unchanged and increased again during the second year of life, indicating a decreased affinity of the receptor sites for the ligand. The general properties of the binding; potentiation by glutamate and NMDA, as well as by glycine in a strychnine-insensitive manner, prevailed during development and ageing, certain of these effects being however less pronounced in the immature brain. Taurine and beta-alanine stimulated TCP binding, acting probably at the glycine modulatory site. The actions of these inhibitory amino acids were weak and inconsistent when compared to that of glycine. Since NMDA receptors have been suggested to be involved in neuronal plasticity and learning and memory processes, these modifications in the properties of cortical phencyclidine-binding sites might be of importance in the regulation of excitatory amino acid functions during development and ageing.

Aging↗
PubMed1993

Uptake and release of beta-alanine in cerebellar granule cells in primary culture: regulation of release by glutamatergic and GABAergic receptors.

The uptake and release of beta-[3H]alanine were studied in cultured glutamatergic cerebellar granule cells of the rat. The uptake of beta-alanine was saturable and sodium-dependent, comprising one high-affinity transport component. It was inhibited by hypotaurine, taurine, GABA and homotaurine but not by glycine or glutamate. The release was enhanced by homoexchange, veratridine and high K+ concentrations (50 mM). The K(+)-stimulated release was at least partially Ca(2+)-dependent. The release was shown to be subject to regulation by GABAA receptors and glutamate receptors of the kainate type. The results signify that beta-alanine may have a functional role in cerebellar granule cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Release of GABA from rat hippocampal slices: involvement of quisqualate/N-methyl-D-aspartate-gated ionophores and extracellular magnesium.

Effects of glutamate agonists and their selective antagonists on the Ca(2+)-dependent release of [3H]GABA from rat hippocampal slices were studied in a superfusion system. The release was enhanced by glutamate, kainate, quisqualate, N-methyl-D-aspartate and glycine in a concentration-dependent manner. In general, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801) strongly antagonized the effects of all agonists tested in low-Mg2+ (0.1 mM) media. 6-Cyano-7-nitroquinoxaline-2,3-dione did not inhibit the effects of N-methyl-D-aspartate, quisqualate, glycine or N-methyl-D-aspartate together with glycine in 0.1 mM Mg2+ media. Extracellular Mg2+ failed to block the release elicited by the agonists alone. However, the action of N-methyl-D-aspartate was potentiated by glycine only in low-Mg2+ media. We suggest that under the present experimental conditions the activation of N-methyl-D-aspartate/low-affinity quisqualate receptors located presynaptically on excitatory fibre terminals and/or postsynaptically on GABAergic interneurons is essential in hippocampal GABA release. A functional interaction is proposed between glycine and extracellular Mg2+ in the modulation of the quisqualate N-methyl-D-aspartate-gated ionophores involved in this process.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Modulation of glutamate agonist-induced influx of calcium into neurons by gamma-L-glutamyl and beta-L-aspartyl dipeptides.

Gamma-L-Glutamate and beta-L-aspartate dipeptides, present in the mammalian brain with a yet unknown function, were shown to affect the influx of Ca2+ into cultured cerebellar granule cells. The most active peptides, gamma-L-glutamyl-L-aspartate, gamma-L-glutamyl-L-glutamate and gamma-L-glutamylglycine, enhanced the basal influx but inhibited the glutamate-activated influx of Ca2+ in a dose-dependent manner. Gamma-L-Glutamyl-L-aspartate, the strongest inhibitor of the glutamate-activated influx of Ca2+, exhibited selective Mg(2+)-dependent antagonism in the N-methyl-D-aspartate (NMDA)-activated influx of Ca2+. This finding may explain its previously shown deleterious effects on the long-term memory. On the other hand, gamma-L-glutamyl-L-aspartate enhanced alone the entry of Ca2+ into neurons. This effect was antagonized by the non-NMDA antagonists 6-nitro-7-cyanoquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), suggesting a non-NMDA receptor-mediated action, that may also be involved in excitotoxicity in some neurodegenerative disorders.

Animals↗
PubMed1992

Taurine release and swelling of cerebral cortex slices from adult and developing mice in media of different ionic compositions.

The release of preloaded radiolabeled taurine was studied in superfused cerebral cortex slices obtained from adult and 3-day-old mice in media of varying ionic composition. Our aim was to establish whether the release of taurine from slices evokable by high concentrations of K+ could be attributed solely to cell volume changes or whether it results directly from depolarization of cell membranes. In both age groups hypoosmotic media enhanced the release of taurine. The enhancement was greater in 3-day-old than in adult mice. The K(+)-evoked release of taurine was likewise greater in slices from 3-day-old mice than in slices from adult mice. The K+ stimulation was totally preserved in adult mice and partially preserved in 3-day-old mice when the slices were superfused with Cl(-)-free media, with media in which the K+ x Cl- ionic product was kept constant and with hyperosmotic high-K+ media. The results were practically the same when the permeant anion acetate and the impermeant anion gluconate were used to replace the Cl- deficit. The unstimulated release of preloaded taurine was greatly enhanced in Cl(-)-free media in both age groups. There obtained no statistically significant correlation between the intracellular swelling of slices and the magnitude of taurine release under the present different experimental conditions in either age group. The results show that the K(+)-evoked release of taurine from superfused cerebral cortex slices cannot be solely attributed to depolarization-induced cell swelling. At least a part of the release results directly from membrane depolarization which besides exocytosis apparently also enhances the carrier-mediated release of taurine and inhibits the reuptake of taurine liberated from intracellular compartments.

Aging↗
PubMed1992

Enhanced GABA release in cerebral cortical slices derived from rats with thioacetamide-induced hepatic encephalopathy.

The release of newly loaded [3H]GABA was studied in slices of different brain regions derived from rats in which acute hepatic encephalopathy (HE) was induced with a hepatotoxin thioacetamide. HE increased both spontaneous and high (50 mM) ammonium chloride-evoked GABA release in cerebral cortical slices by 38% and 50%, respectively. No effects of HE were noted in cerebellar or striatal slices. An increased release of GABA in the cerebral cortex may contribute to the endogenous benzodiazepine-mediated enhancement of GABAergic tone, which is thought to be partly responsible for the pathophysiological mechanism of HE.

Ammonium Chloride↗