摘要:

Abstract—1. Whereas exogenousl‐glutamate enters rat brain cortex slices incubated in a glucose‐physiological saline medium by both low affinity (Km= 0.7 mm) and high affinity (Km= 27−30 μM) processes, the uptake ofd‐glutamate occurs only by a low affinity (Km= 2mm) system. 2.d‐glutamate appears to releasel‐glutamate from incubated rat brain cortex slices only to a very small extent, whether the tissuel‐glutamate is of endogenous or exogenous origin. 3. Competitive inhibition takes place betweenl‐ andd‐glutamates at the low affinity carrier. This indicates that a common carrier exists forl‐ andd‐glutamates for the low affinity uptake process. 4. Apparently non‐competitive inhibition byd‐glutamate ofl‐glutamate uptake occurs at the high affinity carrier, but the affinity ofd‐glutamate for this carrier is about 0.4% of that ofl‐glutamate. 5. Bothd‐, andl‐glutamate exchange freely with labelledd‐glutamate taken up by preliminary incubation of the brain slices with this amino acid. Whereasl‐glutamate exchanges freely with labelledl‐glutamate taken up by preliminary incubation,d‐glutamate shows little or no exchange. 6. The uptake of labelledd‐glutamate by exchange diffusion into brain slices previously loaded with unlabelledd‐glutamate proceeds by a low affinity system. Therefore, the process of exchange diffusion does not necessarily involve a high affinity uptake component. 7. Whereas ouabain suppresses both high and low affinity concentrative uptakes ofl‐ andd‐glutamate it has little apparent effect on the exchange diffusion process. 8. Sensitivity to tetrodotoxin of evoked release ofl‐ andd‐glutamates, taken up by brain slices by preliminary incubation with these amino acids, indicates that the major proportion of the uptake of exogenousl‐ ord‐glutamate proceeds into non‐neuronal structures (presumably the glia). 9. At 0°C non‐carrier mediated (passive)

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01493.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—The effects of exposure to an antithyroid drug, methimazole, on brain tyrosine hydroxylase and tryptophan hydroxylase activity, as well as the levels of norepinephrine, dopamine, 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid have been investigated in maturing brain. Daily treatment of neonatal rats with methimazole for 30 days induced chemical thyroidectomy as evidenced by significant impairment of body and brain growth. The activities or brain tyrosine hydroxylase and tryptophan hydroxylase and the levels of norepinephrine, dopamine and 5‐hydroxytryptamine were markedly altered in a dose‐ and time‐dependent manner in methimazole‐treated rats. Conversely, the concentration of brain 5‐hydroxyindoleacetic acid was elevated (46%) by methimazole administration. Treatment with the antithyroid drug failed to exert any significant effect on the endogenous levels of brain tryptophan, as well as on the activity of the deaminating enzyme, monoamine oxidase. Administration of triiodothyronine (25 or 100 μg/100 g) to hypothyroid rats for 30 days did not produce any appreciable effect upon the neurochemical parameters related to either norepinephrine or 5‐hydroxytryptamine mctabolism. However, increasing the dose of triiodothyronine to 250 μg/100 g significantly elevated the levels of norepinephrine and 5‐hydroxytryplamine as well as the activities of the two synthesizing enzymes, tyrosine hydroxylase and tryptophan hydroxylase. Brain 5‐hydroxyindoleacetic acid levels were restored to normal values in thyroid hormone‐deficient rats treated with this higher dose of triiodothyronine. Evidencc also was obtained to show that chemical thyroidectomy suppressed the spontancous locomotor activity in neonatal rats; the changes being apparent at 15 days of age. Our data support the view that thyroid hormone in neonatal life displays an important regulatory effect on the metabolism of norepinephrine, dopamine and 5‐hydroxytryptamine. Since certain amines have been known to be implicated as the neurochemical substrates for behavioural arousal, it is conceivable that the observed hypoactivity in methimazolc‐treated rats may, at least in part, be related to impaired maturation of norepinephrine and dopamine‐synthesizing syst

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01494.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—Ataxic and non‐ataxic lambs reared under field conditions which gave rise to low copper status were treated with copper intravenously. Untreated ataxic animals served as controls. The neurotransmitter amines, dopamine, norepinephrine and serotonin, were determined in the anterior and posterior regions of the brain stem. Dopamine levels in the anterior region, including the corpus striatum, were significantly lower in the untreated animals than in those treated with copper. Norepinephrine levels were also lower but serotonin concentrations were not different. Plasma amine oxidase activity was markedly higher in the copper treated animals but monoamine oxidase activity in brain stem homogenates was not significantly affected. The monoamine oxidase activity in cortical and cerebellar homogenates was significantly lower in the treated animals than in the untreated anim

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01495.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—The concentration of cystathionine, along with the specific activities of the enzymes involved in its synthesis and degradation, cystathionine synthasc and cystathionase, respectively, have been measured in brain, liver and kidney of the developing Rhesus monkey from mid‐gestation, through birth and neonatal life, to maturity. The concentration of cystathionine and the specific activity of cystathionine synthase are low in fetal brain. Both parameters increase slowly after birth and reach values found in adult brain at approx 3 months of postnatal age. The activity of cystathionase in brain is low throughout development.Liver provides a direct contrast in that the concentration of cystathionine and the specific activity of cystathionine synthase are high in the fetus, decreasing rapidly after birth to values found in the adult by 2 weeks of postnatal age. Cystathionase activity is low in fetal liver and increases slowly after birth reaching values found in adult liver after 2–3 months. Kidney has no more than trace amounts of cystathionine throughout development, higher activity of cystathionine synthase in the fetus than in the adult and high, unchanged activity of cystathionase throughout the period of development studied.These results indicate that the high concentrations of cystathionine found in primate brain are reached postnatally and suggest that this high concentration of cystathionine may be associated with the functioning of mature

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01496.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—A neuroblastoma adrenergic clone M1, which multiplies rapidly in vitro, can be induced to differentiate by addition of bromodeoxyuridine to the proliferating cells. In parallel to higher oxygen uptake, a progressive decrease of the activities of aldolase and lactate dehydrogenase is observed in BrdU treated cells. Other enzymic activities involved in carbohydrate metabolism are not substantially modified. The change in the lactate dehydrogenase isoenzyme pattern usually observed in neuroblastoma M1 cells during the different growth phases is abolished by the bromodeoxyuridine treatment. The mechanism of the inhibitory effect of bromodeoxyuridine is discusse

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01497.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—A method was developed to measure small amounts of dopamine or norepincphrine in biological samples. It was based on the radioenzymic assay originally described by Engelmanet al.(1968) and improved by other workers: dopamine and norepinephrine areO‐methylated by catechol‐O‐ methyl‐transferase in the presence of [3H]S‐adenosylmethioniiie as la belled methyl donor.O‐Methylated derivatives are extracted and estimated. The optimal conditions for theO‐methylation and the extractions were determined. The most important improvement in the method consisted in the selective isolation of catecholamines on microcolumns of alumina under conditions that allowed their subsequent enzymic assay. The assay described can thus be used on any size of biological sample. The assay was not affected by the prescnce of various agents (tissue extracts, CSF salts and particularly calcium, drugs etc.) which were shown to interfere with theO‐methylation process, and it allowed the measurement of quantities of dopamine and norepinephrine as low as 0.15 and 0.1 pmol respectively, whatever the origin of the sample (CSF superfusates,

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01498.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—In piglets affected with congenital tremor type AII the CNS was not morphologically underdeveloped; spinal cord weight, total DNA content and fat‐free dry matter differed little from control values. However the total lipid extractable from affected spinal cords was only about 63% of values established for normal newborn piglets. In particular, the cerebroside content (a myelin‐specific lipid) was reduced to about 30% of the ‘normal’ value. This was parallelled by the results of anin vitroassay of cerebroside synthesis from [3H]galactose which indicated a metabolic impairment. The altered fatty acid profile of isolatcd cerebrosides further suggested a derangement of fatty acid synthesis. Unlike the spinal cords of normal newborn piglets, tissues from affected piglets contained significant amounts of cholesterol esters carrying the characteristic fatty acids associated with demyelination. This implied that the reduced quantities of possibly abnormal myelin were unstable. Abnormal swollen oligodendrocytes were commonly present in the spinal cords of affected piglets and this was consistcnt with the observed impairment of myelin

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01499.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—Thin sections prepared from the olfactory cortex of the guinea pig were incubated in a medium containing [14C]glutamate, and release of radioactive compounds and electrical activity were subsequently examined in the presence ofl‐cysteate. The postsynaptic potential was almost completely suppressed in the medium containingl‐cysteate, whereas the presynaptic potential was unaffected. Repetitive stimulation of the excitatory input of the lateral olfactory tract enhanced release of radioactive glutamate. The facilitatory effect of lateral olfactory tract stimulation increased with increase in stimulus frequency and was dependent on calcium. Release of radioactive gluiamine was not enhanced by lateral olfactory tract stimulation. Phenobarbitone sodium markedly depressed both the postsynaptic potential and the effect of lateral olfactory tract stimulation on glutamate release. These results indicate that stimulation to the lateral olfactory tract enhances liberation of glutamate from the tract nerve term

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01500.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—Particulate fractions from rat brain homogenate containing the synaptosomes synthesize and release prostaglandins F and E on aerobic incubation. The prostaglandin of the F‐typc released could be further identified as proslaglandin F2αusing specific radioimmunoassays for prostaglandins F1α, and F2α‐. The metabolite 13,14‐dihydro‐15‐keto‐prostaglandin F2αcould not be detected. The amount of prostaglandins released is dependent on incubation time and temperature as well as pH and osmolarity of the incubation medium. Total brain homogenate released more prostaglandins than purified synaptosomes per mg protein, indicating that synaptosomes are probably not a main source of prostaglandins when compared with other subcellular brain fractions. While prostaglandin synthesis was only moderately increased by the addition of the precursor fatty acid arachidonic acid, anti‐inflammatory drugs like indomethacin, high concentrations of some local anaesthetics and Δ1‐tetrahydrocannabinol inhibited prostaglandin release. The neurotransmitters noradrenaline, dopamine and 5‐hydroxytryptamine did not influence prostaglandin release from the synaptos

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01501.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

Abstract—Sulfated galactocerebroside synthesis was examinedin vitroin mouse spinal cord cultures. This system permitted the study of the effects of phenylketonuric metabolites upon synthesis of a specific myelin component, sulfatide, formed early in postnatal development in mice. A significant reduction of Na235SO4incorporation into myelin sulfatide was observed when spinal cord cultures were grown in the presence of 1000 μm‐l‐phenylalanine and 500 μm‐phenylpyruvate (51 and 700%, respectively). No reduction was observed with β‐phenyllactate (300 μmand) phenylacetate (250 μm). Light microscopy indicated that the phenylpyruvate and phenylalanine treated cultures were less extensively myelinated compared to control and β‐phenyllactate or phenylacetate treated cultures. The reduction of sulfatide synthesis by phenylpyruvate was shown to be reversible.Intracerebral bilateral injections (8 μg) ofl‐phenylalanine, phenylpyruvate, α‐ketobutyrate, α‐ketoisocaproate, α‐ketoisovalerate, β‐phenyllactate, and phenylacetate in mice 8–15 days old, followed by i.p. administration of radioactive sulfate, resulted in significantly reduced incorporation (allP<0.05) of sulfate into brain sulfatides with all compounds tested with the exception of β‐phenyllactate and phenylacetate. In adult mouse, phenylpyruvate treatment also resulted in a significant decrease in labelling of brain sulfatide.The effects of phenylpyruvate and other metabolites upon pyruvate oxidation in mouse brain homogenates were examined by measuring14CO2release from [1‐14C]pyruvate. Both phenylpyruvate and α‐ketoisocaproate at 1 × 10‐3resulted in a decrease in14CO2produced, while phenylacetate and β‐phenyllactate had no effect.Sulfate incorporation into sulfatide was reduced by α‐ketoisocaproate and phenylpyruvate, and to a lesser extent by phenylalanine, α‐ketobutyrate, and α‐ketoisovalerate. Phenyllactate and phenylacetate had no effect, eitherin vivo, or in culture. This order of effectiveness may be related in par

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1976.tb01502.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY