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S S Oja

Publications and source records attributed to S S Oja.

At least 73 records · Page 4Linked to original sources
PubMed1997

Taurine release from the developing and ageing hippocampus: stimulation by agonists of ionotropic glutamate receptors.

The inhibitory amino acid taurine has been held to function as a modulator and osmoregulator in the brain, being of particular importance in the immature brain. The release of preloaded [3H]taurine was now studied in hippocampal slices from developing (7-day-old), adult (3-month-old) and ageing (6-24-month-old) mice focussing on the effects of agonists of ionotropic glutamate receptors. N-methyl-D-aspartate (NMDA), kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release concentration-dependently at each age, more so in the immature than in the adult and ageing hippocampus. The effect of kainate was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the developing and aged hippocampus and those of AMPA and NMDA by 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and dizocilpine a(MK-801) at every age studied. This indicates the involvement of NMDA and AMPA receptors in taurine release throughout the life-span of mice, while the kainate-receptor-mediated release does not appear to function in adults. The increased hippocampal taurine release evoked by ionotropic glutamate receptors could act neuroprotectively, counteracting by several mechanisms the harmful effects of the simultaneous release of excitatory amino acids. The substantial release of taurine in the immature hippocampus might be particularly significant in view of the vulnerability of brain tissue to excitotoxicity at early age.

Aging↗
PubMed1997

Ligand binding to porcine ionotropic glutamate receptors with chemically modified arginyl residues.

The involvement of arginyl residues in the binding of ligands to different ionotropic glutamate receptors, to the modulatory glycine site in the N-methyl-D-aspartate (NMDA) receptor and to the NMDA-governed ionophore was assessed with porcine cortical synaptic membranes. The arginyl residues were covalently modified with phenylglyoxal. The binding and protection experiments showed that arginine residue(s) are directly involved in the binding of ligands to the agonist sites of all ionotropic glutamate receptors and to the modulatory glycine site but not to the ion channel in the NMDA receptor complex.

Animals↗
PubMed1997

Role of histidyl residues in the binding of ligands to the porcine N-methyl-D-aspartate receptor.

Possible involvement of histidyl residues in the binding of ligands to ionotropic glutamate receptors and to modulatory sites on the N-methyl-D-aspartate (NMDA) receptor was assessed in porcine cortical synaptic plasma membranes after covalent modification with diethyl pyrocarbonate (DEPC). Binding of [3H]glutamate to the NMDA sites was enhanced but to the 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate receptors unaffected by 1 and 5 mM DEPC. Binding of 3-[(R)-carboxypiperazin-4-yl]-[1,2-(3)H]propyl-1-phosphonate ([3H]CPP) was reduced in a dose-dependent manner by DEPC and the activation of binding by 1-hydroxy-3-amino-2-pyrrolidone (HA-966) blocked by 10 mM DEPC. DEPC reduced the strychnine-insensitive binding of [3H]glycine and the glycine- and glutamate-activated binding of [3H]dizocilpine. Protection experiments indicated that histidyl residues are directly involved in the binding of glycine (but not HA-966) and allosterically modulate the binding of glutamate, CPP and dizocilpine. The results corroborate the existence of agonist- and antagonist-preferring sites or conformational states of the NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1997

Enhanced taurine release in cell-damaging conditions in the developing and ageing mouse hippocampus.

Taurine has been shown to be essential for neuronal development and survival in the central nervous system. The release of preloaded [3H]taurine was studied in hippocampal slices from seven-day-, three-month- and 18-22-month-old mice in cell-damaging conditions. The slices were superfused in hypoxic, hypoglycemic and ischemic conditions and exposed to free radicals and oxidative stress. The release of taurine was greatly enhanced in the above conditions in all age groups, except in oxidative stress. The release was large in ischemia, particularly in the hippocampus of aged mice. Potassium stimulation was still able to release taurine in cell-damaging conditions in immature mice, whereas in adult and aged animals the release was so substantial that this additional stimulus failed to work. Taurine release was partially Ca2+-dependent in all cases. The massive release of the inhibitory amino acid taurine in ischemic conditions could act neuroprotectively, counteracting in several ways the effects of simultaneous release of excitatory amino acids. This protection could be of great importance in developing brain tissue, while also having an effect in aged brains.

Aging↗
PubMed1997

Enhanced GABA release in cell-damaging conditions in the adult and developing mouse hippocampus.

The release of [3H]GABA from hippocampal slices from adult (3-month-old) and developing (7-day-old) mice was studied in cell-damaging conditions in vitro using a superfusion system. Cell damage was induced by modified superfusion media, including hypoxia, hypoglycemia, ischemia, the presence of Free radicals and oxidative stress. The basal release of GABA from the immature and mature hippocampus was generally markedly increased in all cell-damaging conditions. In 7-day-old mice the release was enhanced most in the presence of free radicals. 1.0 mM NaCN and ischemia, whereas in the adults 1.0 mM NaCN provoked the largest release of GABA, followed by ischemia and free radical-containing media. Potassium stimulation (50 mM K+) was still able to potentiate the release in all cell-damaging conditions in both age groups. It was shown by superfusing the slices in Ca- and Na-free media that ischemia-induced GABA release was Ca-independent, occurring by a reversed operation of Na-dependent cell membrane carriers in both adult and developing hippocampus. Glutamate and its receptor agonists, N-methyl-D-aspartate (NMDA), kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), potentiated GABA release only in the immature hippocampus by a receptor-mediated mechanism. The enhancement by kainate and AMPA receptors also operated under ischemic conditions. The massive amount of GABA released simultaneously with excitatory amino acids in the mature and immature hippocampus may be an important protective mechanism against excitotoxicity, counteracting harmful effects that lead to neuronal death. The GABA release induced by activation of presynaptic glutamate receptors may contribute particularly to the maintenance of homeostasis in the hippocampus upon impending hyperexcitation.

Animals↗
PubMed1997

Release of [3H]dopamine from striatal and cerebral cortical slices from rats with thioacetamide-induced hepatic encephalopathy: different responses to stimulation by potassium ions and agonists of ionotropic glutamate receptors.

The effects of depolarizing stimuli; high (50 mM) potassium ions and the glutamate receptor agonists N-methyl-D-aspartate, kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) on the release of newly-loaded [3H]dopamine were studied in frontal cortical and striatal slices from control rats and from rats with acute hepatic encephalopathy induced with a hepatotoxin, thioacetamide. Hepatic encephalopathy enhanced the stimulatory effect of potassium ions by 20% in striatal slices and by 34% in frontal cortical slices. In striatal slices the stimulatory effects of N-methyl-D-aspartate and kainate were depressed in hepatic encephalopathy by 46% and 21%, respectively, which may be taken to reflect impaired modulation of striatal dopamine release by glutamate acting at N-methyl-D-aspartate or kainate receptors. In frontal cortical slices, the stimulatory effect of kainate was enhanced by 35% in hepatic encephalopathy but N-methyl-D-aspartate-stimulated release was not affected. The release evoked by 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate was not affected in hepatic encephalopathy in either brain region. Stimulation of dopamine release in the frontal cortex by depolarization or glutamate acting at kainate receptors could inhibit the activity of descending corticostriatal glutamatergic pathways, further impairing regulation of dopamine release by glutamate in the striatum.

Animals↗
PubMed1997

Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors.

A study was made of the effects of reduced (GSH) and oxidized (GSSG) glutathione on the Na(+)-independent and N-methyl-D-aspartate (NMDA) displaceable bindings of glutamate, on the binding of kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and ligand of the brain NMDA receptor-ionophore complex: glycine, dizocilpine (MK-801) and (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP). GSH and GSSG strongly inhibited the binding of glutamate, CPP and AMPA, kainate and glycine binding being less affected. Both peptides enhanced the binding of dizocilpine in a time- and concentration-dependent manner. This activatory effect was not additive to that of saturating concentrations of glutamate or glutamate plus glycine. The activation of dizocilpine binding by GSH and GSSG was prevented by the competitive NMDA and glycine antagonists DL-2-amino-5-phosphonovalerate and 7-chlorokynurenate. GSH and GSSG may be endogenous ligands of AMPA and NMDA receptors, binding preferably to the glutamate recognition site via their gamma-glutamyl moieties. In addition to this, at millimolar concentrations they may regulate the redox state of the NMDA receptor-ionophore complex.

Animals↗
PubMed1997

Leucine supplementation and serum amino acids, testosterone, cortisol and growth hormone in male power athletes during training.

OBJECTIVE: The purpose of the present study was to examine the effects of leucine supplementation on the amino acid and hormone profile during training. EXPERIMENTAL DESIGN: The study was a randomised double-blind cross-over study during 10 weeks of training. SETTING: The study occurred during a sport training period. PARTICIPANTS: Twenty adult male track and field power athletes finished the study. INTERVENTIONS: The subjects were given leucine (50.0 +/- 3.3 mg/ kg body weight per day) or placebo tablets. MEASUREMENTS: The measurements were carried out before, in the middle of, and after 10 weeks. RESULTS: The serum leucine concentration decreased significantly (p < 0.05) in the placebo group, by 20.1% (from 189 +/- 45 to 151 +/- 21 mumol/l) during the first 5 weeks, but not during the second 5 weeks (180 +/- 61 vs 154 +/- 23 mumol/l). When leucine was taken there were no changes in the serum leucine concentration. The total serum amino acid pool decreased significantly (p < 0.01) in all subjects, by 21.2% during the 10-week training period. The decrease occurred mostly during the first 5 weeks. Glutamine decreased (37.1%; p < 0.01) most of the single amino acids. The serum testosterone concentration increased by 20.7% (p < 0.05) and the serum cortisol concentration by 8.0% (p < 0.05) in all subjects during the first 5 weeks. During the second 5 weeks the testosterone concentration decreased by 19.0% (p < 0.001). CONCLUSIONS: The present findings indicate that on a daily protein intake of 1.26 g/kg body weight the serum concentrations of amino acids are lowered considerably and earlier than the decrease in the serum testosterone concentration during the training season in adult male power athletes. The leucine supplementation of 50 mg/kg body weight per day appears to prevent the decrease in the serum leucine concentration during intensive training.

Adult↗
PubMed1996

Taurine as osmoregulator and neuromodulator in the brain.

Taurine has been assumed to function as an osmoregulator and neuromodulator in the brain. The pertinent studies are now reviewed in an attempt to formulate a unifying hypothesis as to how taurine could simultaneously act in both roles. Neuromodulatory actions of taurine may also underlie its protective effects against neuronal overexcitation and glutamate agonist-induced neurotoxicity.

Animals↗
PubMed1996

Kinetic analysis of taurine influx into cerebral cortical slices from adult and developing mice in different incubation conditions.

The influx of taurine into cerebral cortical slices was studied with 3-day-old and 3-month-old mice in different ionic environments in incubation medium. In standard Krebs-Ringer medium the influx comprised two saturable uptake components, high- and low-affinity, and non-saturable penetration. In isoosmotic medium potassium stimulation abolished the high-affinity uptake in both age groups. In hyperosmotic medium the high-affinity uptake disappeared totally in 3-day-old mice and partially in 3-month-old mice. The high-affinity uptake was also obliterated in hypoosmotic medium and in the absence of chloride ions in both age groups. The low-affinity uptake was abolished by potassium stimulation in 3-month-olds and strongly inhibited in 3-day-olds. Hypoosmotic and chloride-free media also inhibited the low-affinity uptake at both ages. Non-saturable influx was greatly diminished in chloride-free media. The taurine uptake systems are thus strongly inhibited in incubation conditions which simultaneously evoke apparent release of taurine from cerebral cortical slices. This inhibition contributes to the magnitude of the estimated release, which in vitro represents overflow of released taurine molecules which escape recapture by the membrane carriers. In vivo the same mechanism may underlie the delayed and spreading neuromodulatory actions of taurine.

Animals↗
PubMed1996

Simultaneous detection of action potential current waveforms and single ion channel openings in rat cerebellar granule cells.

Spontaneous Action Potential Current waveforms (APCs) and single ion channel openings were recorded in cultured rat cerebellar granule cells using the cell-attached configuration of the patch-clamp technique. APCs were activated without any externally applied stimuli. Both mono- and biphasic APCs were detected with a typical amplitude (positive waveform component) of 25-60 pA. Correlation between cell APCs and inward and outward single ion channel openings immediately before and after the capacitive transients was analyzed. In a detailed analysis it was found that the opening of 1.5 pA inward channel before the waveform was associated with 16%, and the opening of 1.0 pA outward channel after the waveform with 88% of APCs (of total 327 APCs analyzed). The modulation of APC activity by bath application of the amino acid taurine was found to increase the frequency of APCs, transform the APCs from mixed monophasic/biphasic to completely biphasic, and enhance the activated inward current deflections seemingly connected to the increased firing frequency.

Action Potentials↗