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Biomedical subjects

S S Oja

Publications and source records attributed to S S Oja.

At least 91 records · Page 5Linked to original sources
PubMed1995

Dizocilpine binding to cerebral cortical membranes from developing and ageing mice.

The binding of [3H]dizocilpine (MK-801) to the N-methyl-D-aspartate (NMDA)-gated ion channel was characterized in cerebral cortical membranes during the major portion of the mouse life-span (from 7-day- to 22-month-olds). The binding was saturable, consisting of only one component at all ages studied. The maximal binding capacity Bmax was very substantial in 14-day-old mice when compared to adults (3-month-olds), decreasing thereafter during ageing. The binding constant KD remained unchanged during development and increased only slightly in aged mice. Glutamate and glycine potentiated dizocilpine binding concentration-dependently. Their efficacy varied markedly with age. Both glutamate and glycine had considerably less effect on the immature cerebral cortex and in the oldest group of mice (22-month-old) than in young adults. The marked increase in dizocilpine binding sites at the age of 2 weeks coincides with the previously reported transient increase in NMDA binding sites in the cerebral cortex. The weak potentiation of dizocilpine binding by glutamate and glycine in the immature brain could be a factor which protects neurons during this period from excitotoxicity and increased susceptibility to seizures induced by acidic amino acids. The decrease in the number of dizocilpine binding sites during ageing could result partly from the loss of cortical neurons.

Age Factors↗
PubMed1995

Age-related changes in the uptake and release of glutamate and aspartate in the mouse brain.

The studies were carried out on 3- and 7-day, 3-, 6-, 12-, 18- and 24-month-old mice. The levels of glutamate and aspartate increased in most brain areas in developing mice and then decreased gradually during ageing, the changes depending, however, on the brain region. The maximal velocity (V) of high-affinity uptake of [3H]glutamate was markedly reduced in cerebral cortical synaptosomes at the age of 24 months, indicating an age-related loss in the number of transport sites. The transport constant (Km) was also diminished in aged mice, indicating a compensatory increase in the affinity of the remaining transport sites. The basal and K(+)-stimulated (50 mM) release of endogenous glutamate and aspartate varied depending on the brain region. The responses to K+ stimulation generally increased during maturation, whereas the other age-related changes were more variable. The basal unstimulated release of glutamate remained fairly constant in the cerebral cortex during ageing, but K+ depolarization liberated more glutamate in 24-month-olds than in 3-month-olds. The decreased uptake capacity together with an increased release of glutamate may contribute to the degenerative changes associated with normal brain ageing and also to the pathogenesis of age-related neurodegenerative disorders.

Aging↗
PubMed1995

Endogenous gamma-L-glutamylglutamate is a partial agonist at the N-methyl-D-aspartate receptors in cultured cerebellar granule cells.

gamma-L-Glutamylglutamate (LGG), an endogenous constituent of the brain, reduced the glutamate-evoked increase in intracellular Ca2+ in cultured cerebellar granule cells. The extent and properties of this inhibition were different at different Mg2+ concentrations. The intracellular Ca2+ response to NMDA was slightly enhanced by 0.1 mM LGG in normal (1.3 mM) Mg2+ medium, but in Mg(2+)-free medium LGG was stimulatory at low (0.1-1 microM) NMDA and inhibitory at high (0.1-1 mM) NMDA concentrations. In the absence of Mg2+, LGG alone increased cytosolic free Ca2+ and depolarized the cells. These effects were potentiated by glycine and blocked by extracellular Mg2+, 2-amino-5-phosphonopentanoate (APV), 7-chlorokynurenate, 3-amino-1-hydroxypyrrolidin-2-one (HA-966) and 5,7-dinitroquinoxaline-2,3-dione (MNQX). The results indicate that LGG is a partial NMDA agonist. On the other hand, the non-NMDA antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) also inhibited the effects of LGG. This indicates an involvement of non-NMDA receptors in the actions of LGG. The consequent depolarization may also contribute to the activation of NMDA receptor-governed ionophores.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy.

OBJECTIVE: To determine the antigenicity, nutritional adequacy, and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy. STUDY DESIGN: Several protein hydrolysate or amino acid-derived formulas were graded for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind, placebo-controlled challenge. A randomized, prospective follow-up study of 9 months included 22 infants with a mean age of 6 months (95% confidence interval, 4 to 7), who were fed an extensively hydrolyzed whey formula (group We), and 23 infants with a mean age of 17 (95% confidence interval, 4 to 7) months, who were given an amino acid-derived formula (group AA). RESULTS: Both formulas were clinically and biochemically tolerated. The mean concentration of essential amino acids in plasma was lower in group We but higher in group AA compared with values for breast-fed control infants (p = 0.001). There was a different trend between the groups in weight (p = 0.09) and length (p = 0.006). Growth was promoted in group AA during the follow-up; it was constant during the first months, followed by a gradual decline in rate in group We. In both groups, atopic eczema improved significantly and progressively, and a downward trend was found in serum total and milk-specific IgE concentrations, proving the efficacy of both formulas. CONCLUSIONS: Extensively hydrolyzed formulas are safe and effective for most infants; an amino acid-derived formula may be preferable for infants with multiple food allergies, especially for the maintenance of normal growth.

Amino Acids↗
PubMed1995

The effect of phencyclidine on [3H]GABA and [3H]flunitrazepam binding in the brain of naive and handling-habituated rats.

The effects of handling and handling combined with phencyclidine (PCP) treatment on GABAergic neurotransmission were studied in Sprague-Dawley rats. The animal material consisted of handling-habituated (HH, for 11 d), acutely handled (naive, N), handling-habituated and PCP-treated (10 mg kg-1 i.p., HH + PCP) and acutely handled (naive) PCP-treated (N + PCP) and unhandled 'control' rats. The binding of [3H]GABA and [3H]flunitrazepam (FLU) was studied with membranes and the release of [3H]GABA with slices prepared from the striatum and frontal cortex. In the striatum the maximal binding capacity (Bmax) and the binding constant (KD) of [3H]GABA were the same in N and HH rats, but in the frontal cortex KD was lower in N rats. KD constants of [3H]FLU were significantly lower in both brain areas in N rats than in HH rats. After PCP treatment both Bmax and KD for [3H]FLU increased in these two brain areas in handling-habituated rats, whereas Bmax of [3H]GABA diminished. Neither handling nor PCP had any effect on [3H]GABA release from striatal and frontal cortical slices. Handling prior to killing thus affects differently the GABAergic parameters studied and modulates the PCP-induced effects.

Animals↗
PubMed1994

Glycine release from hippocampal slices in developing and ageing mice: modulation by glutamatergic receptors.

The release of preloaded [3H]glycine from hippocampal slices in developing and ageing mice (from 7 days to 22 months) was characterized using a superfusion system. The release was Ca(2+)-independent in each age group studied. The basal release and the responses to potassium stimulation were fairly constant during the whole life span. The release was potentiated by the glutamate receptor agonists kainate, N-methyl-D-aspartate (NMDA), tetrazolylglycine, quisqualate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) in developing mice, but only kainate was effective in adult and aged animals. The kainate effect was not modified by the antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in adult and old mice, indicating that glutamatergic systems may not be involved in the release. On the other hand, hippocampal glycine release in immature mice seems to be subject to regulation by both NMDA and non-NMDA (kainate and AMPA) receptors. The potentiations by NMDA and AMPA were antagonized by dizocilpine (MK-801) and CNQX, respectively. The modulation of glycine release by glutamatergic receptors could be of importance in the regulation of synaptic glycine levels in the developing hippocampus.

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

Taurine in the developing cat: uptake and release in different brain areas.

Taurine is an important modulator of neuronal activity in the immature brain. In kittens, taurine deficiency causes serious dysfunction in the cerebellar and cerebral visual cortex. The processes of taurine transport in vitro were now studied for the first time in different brain areas in developing and adult cats. The uptake of taurine consisted initially of two saturable components, high- and low-affinity, in synaptosomal preparations from the developing cerebral cortex and cerebellum, but the high-affinity uptake component completely disappeared during maturation. The release of both endogenous and preloaded labeled taurine from brain slices measured in a superfusion system was severalfold stimulated with a slow onset by depolarizing K+ (50 mM) concentrations. K+ stimulation released markedly more taurine from the cerebral cortex, cerebellum and brain stem in kittens than in adult cats. The responses were largest in the cerebellum. Both uptake and release of taurine are thus highly efficient in the brain of kittens and may be of significance in view of the vulnerability of cats to taurine deficiency.

Aging↗
PubMed1994

Pharmacological characterization of glutamate binding sites in cultured cerebellar granule cells and cortical astrocytes.

Membranes prepared from cerebellar granule cells and cortical astrocytes exhibited specific, saturable binding of L-[3H]glutamate. The apparent binding constant KD was 135 nM and 393 nM and the maximal binding capacity Bmax 42 and 34 mumol/kg in granule cells and astrocytes, respectively. In granule cells the binding was strongly inhibited by the glutamate receptor agonists kainate, quisqualate, N-methyl-D-aspartate (NMDA), L-homocysteate and ibotenate, and the antagonist DL-5-aminophosphonovalerate. In astrocytes, only quisqualate among these was effective. L-Aspartate, L-cysteate, L-cysteinesulphinate and gamma-D-glutamylglycine were inhibitors in both cell types. The binding was totally displaced in both cell types by L-cysteinesulphinate with IC50 in the micromolar range. In astrocytes the binding was also totally displaced by quisqualate, but in granule cells only partially by NMDA, kainate and quisqualate in turn. It is concluded from the relative potencies of agonists and antagonists in [3H]glutamate binding that cerebellar granule cells express the NMDA, kainate and quisqualate types of the glutamate receptor, while only the quisqualate-sensitive binding seems to be present in cortical astrocytes.

Animals↗
PubMed1994

Glutamate agonists and [3H]GABA release from rat hippocampal slices: involvement of metabotropic glutamate receptors in the quisqualate-evoked release.

The effects of glutamate agonists and their selective antagonists on the Ca(2+)-dependent and independent releases of [3H]GABA from rat coronal hippocampal slices were studied in a superfusion system. The Ca(2+)-dependent release evoked by glutamate, kainate and N-methyl-D-aspartate (NMDA) gradually declined with time despite the continuous presence of the agonists. Quisqualate (QA) caused a sustained release which exhibited no tendency to decline within the 20-min period of stimulation. This release was enhanced in Ca(2+)-free medium. The release evoked by QA in Ca(2+)-containing medium was significantly inhibited by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), showing that QA activates NMDA receptors directly or indirectly through (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. The inhibition of MK-801 was slightly diminished and that of CNQX totally abolished in Ca(2+)-free medium. Verapamil inhibited the QA-activated release in both Ca(2+)-containing and Ca(2+)-free media. The effect of QA but not that of AMPA was blocked in Ca(2+)-free medium by L(+)-2-amino-3-phosphonopropionate (L-AP3), a selective antagonist of the metabotropic glutamate receptor. It is suggested that the sustained release of GABA is also mediated partly by activation of metabotropic receptors and mobilization of Ca2+ form intracellular stores.

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

Interactions of gamma-L-glutamyltaurine with excitatory aminoacidergic neurotransmission.

The in vitro effects of gamma-L-glutamyltaurine on different stages of excitatory aminoacidergic neurotransmission were tested with gamma-D-glutamyltaurine as reference. gamma-L-Glutamyltaurine enhanced the K(+)-stimulated release of [3H]glutamate from cerebral cortical slices (25% at 0.1 mM) and slightly inhibited the uptake by crude brain synaptosomal preparations (about 10% at 1 mM). gamma-L-Glutamyltaurine was also a weak displacer of glutamate and its agonists from their binding sites in brain synaptic membrane preparations, being, however, less selective to quisqualate (QA) sites than gamma-D-glutamyltaurine. The basal influx of Ca2+ into cultured cerebellar granular cells was not affected by 1 mM gamma-L-glutamyltaurine, but the glutamate- and its agonist-activated influx was significantly inhibited in low-Mg2+ (0.1 mM) and Mg(2+)-free media. The glutamate-evoked increase in free intracellular Ca2+ and the kainate-activated formation of cGMP in cerebellar slices were both markedly inhibited by 0.1 mM gamma-L-glutamyltaurine. We propose that gamma-L-glutamyltaurine may act as endogenous modulator in excitatory aminoacidergic neurotransmission.

Aging↗
PubMed1994

Systemic phencyclidine administration is associated with increased dopamine, GABA, and 5-HIAA levels in the dorsolateral striatum of conscious rats: an in vivo microdialysis study.

In vivo microdialysis was used to study the effects of systemically administered phencyclidine (PCP, 10 mg/kg) on the extracellular levels of dopamine, dihydroxyphenylacetate (DOPAC), homovanillate (HVA), 5-hydroxy-indolacetate (5-HIAA), gamma-aminobutyrate (GABA), glutamate, and aspartate in the rat dorsolateral striatum. In order to demarcate the effects of anesthesia, tissue trauma and gliosis, the effect of PCP was studied in both anesthetized rats with long and short probe implantation periods and in conscious rats with a long probe implantation period. PCP significantly increased the extracellular levels of dopamine in all experimental groups, though the post-implantation interval and anesthesia modulated the degree of increase. PCP increased 5-HIAA levels in both conscious and anesthetized rats after a long post-implantation period and HVA only in anesthetized rats after a long post-implantation period. Glutamate, aspartate, and DOPAC were not affected by PCP challenge but our study indicated for the first time that systemic PCP elevates extracellular GABA in conscious rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Endogenous gamma-L-glutamyl and beta-L-aspartyl peptides and excitatory aminoacidergic neurotransmission in the brain.

The effects of gamma-L-glutamyl- and beta-L-aspartyl di- and tripeptides on glutamatergic neurotransmission were tested in vitro. Of the peptides, gamma-L-glutamylglutamate was the most effective inhibitor, comparable to glutamate, of both Na(+)-independent and Cl-/Ca(2+)-activated binding/transport of glutamate. gamma-L-glutamylglutamate was most effective in the midbrain and hypothalamus and gamma-L-glutamylaspartate in the hippocampus when tested on the Na(+)-independent binding. The Cl-/Ca(2+)-dependent binding/transport of glutamate was affected by gamma-glutamylaspartate most strongly in the hippocampus. gamma-L-glutamylglycine and beta-L-aspartylglycine moderately inhibited the Na(+)-dependent uptake of L-glutamate and D-aspartate while the other peptides were only weak inhibitors. Reduced and oxidized glutathione enhanced the uptake of L-glutamate. The K(+)-stimulated release of L-glutamate was enhanced by gamma-L-glutamylglutamate and -aspartate and the release of D-aspartate also by gamma-L-glutamylglycine. The results indicate that both pre- and postsynaptic events in glutamatergic neurotransmission are modulated by these endogenous acidic oligopeptides.

Animals↗