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  • 1
    Electronic Resource
    Electronic Resource
    Sulfate Conjugation of Monoamines in Human Brain: Purification and Some Properties of an Arylamine Sulfotransferase from Cerebral Cortex (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: An arylamine sulfotransferase (PST-M) from human brain cortex that is involved in the formation of O-sulfate esters of monoamines has been purified 272-fold by ammonium sulfate fractionation, gel filtration, DEAE-cellulose ion-exchange chromatography, chromatofocussing, and hydroxyapatite chromatography. A molecular weight of 62,000, pK of pH 5.8, and an optimum pH for the reaction at 7.8–8.0 with respect to tyramines have been determined. This enzyme possesses an extremely high affinity for dopamine and m-tyramine based on the low Km values and is moderately active toward noradrenaline and p-tyramine. Serotonin is a poor substrate. In contrast, another sulfotransferase, PST-P, which has been separated from PST-M and partially purified, exhibited a very high affinity for phenol and nitrophenols but was inactive toward the amine sulfate acceptors. In the human brain the specific activity toward dopamine as well as the ratio of activity toward dopamine/phenol was considerably higher than those for rat, hog, and bovine brains.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1985.tb04070.x
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  • 2
    Electronic Resource
    Electronic Resource
    Neuroprotective Effects of Some Monoamine Oxidase-B Inhibitors Against DSP-4-Induced Noradrenaline Depletion in the Mouse Hippocampus (1994)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 63 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenaline (NA) uptake blocker, is capable of inducing long-lasting depletion of NA in some noradrenergic axon terminals and of subsequently causing cell death to NA neuronal cell bodies in rodents. R(−)-Deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, has been shown to be capable of protecting animals against this DSP-4-induced neuronal degeneration. Its action, however, has been claimed to be unrelated to the inhibition of MAO-B activity but rather due to competition for the NA uptake sites. The effects of several types of MAO inhibitors against DSP-4 toxicity, MAO-B activity both in vivo and in vitro, and NA uptake into the hippocampus have been assessed. N-(2-Hexyl)-N-methylpropargylamine (2-HxMP), a potent MAO-B inhibitor, for example, exerts no appreciable effect on NA uptake but is quite potent in counteracting the NA-depleting effect of DSP-4. Such results rule out the possibility that the neuroprotective effect of the MAO-B inhibitors is due mainly to their effect on NA uptake. The in vitro inhibition of MAO-B activity seems to correlate positively with their neuroprotective effects against DSP-4. In comparison to the MAO-B inhibitors, NA uptake blockers, such as desipramine and S(+)-deprenyl, exhibit relatively low efficacy in protecting the NA axon terminals from the effects of DSP-4-induced damage. The restoration of hippocampal NA levels is significantly enhanced with repeated treatments of R(−)-deprenyl or 2-HxMP even at very low doses following the DSP-4 insult. This suggests that in addition to neuroprotection, these MAO-B inhibitors may rescue some of the noradrenergic axon terminals damaged by DSP-4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.63051820.x
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  • 3
    Electronic Resource
    Electronic Resource
    Deuterium Isotope Effect in γ-Aminobutyric Acid Transamination: Determination of Rate-Limiting Step (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 48 (1987), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The rate of transamination of γ-aminobutyric acid (GABA) catalyzed by hog brain γ-aminobutyrate ami-notransferase was substantially reduced when the hydrogen at the γ-carbon position was replaced by deuterium. The deuterium isotope effect of this reaction has been substantiated by fluorometric, radiometric, and mass spectrometric procedures and assessed kinetically. The ratios of Vmax of the nonlabeled substrate/Vmax of the deuterated substrate obtained under different conditions ranged from 6 to 7. This indicates that the cleavage of the hydrogen from the γ-carbon is the rate-determining step in GABA transamination. Similar isotope effects have also been shown to occur in the peripheral system in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1987.tb04112.x
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  • 4
    Electronic Resource
    Electronic Resource
    Neurochemical and Neuroprotective Effects of Some Aliphatic Propargylamines: New Selective Nonamphetamine-Like Monoamine Oxidase B Inhibitors (1994)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 62 (1994), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Aliphatic N-propargylamines have recently been discovered to be highly potent, selective, and irreversible monoamine oxidase B (MAO-B) inhibitors. N-Methyl-N-(2-pentyl)propargylamine (M-2-PP) and N-methyl-N-(2-hexyl) propargylamine (2-HxMP), for example, are approximately fivefold more potent than I-deprenyl at inhibiting mouse brain MAO-B activity following oral administration. These inhibitors are nonaromatic compounds and are chemically quite different from other known MAO-B inhibitors. Some of their neurochemical and neuroprotective properties have been evaluated and compared with those of I-deprenyl. We have confirmed that these new inhibitors selectively inhibit MAO-B activity both in vitro and in vivo. 2-Phenylethylamine levels were substantially increased following administration of M-2-PP, but the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were not affected except at high, nonselective doses. Chronic oral administration of I-deprenyl and M-2-PP causes selective inhibition of MAO-B activity and increases dopamine levels in mouse caudate. M-2-PP, like I-deprenyl, has been shown to be potent in protecting against MPTP-induced damage in the mouse. N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenaline neurotoxin, is not an MAO substrate. Its noradrenaline-depleting effects were substantially mitigated by I-deprenyl as well as by M-2-PP and 2-HxMP in the mouse hippocampus. Administration of 2-phenylethylamine, however, failed to reverse the effect of DSP-4. The neuroprotective effect of M-2-PP and 2-HxMP is apparently unrelated to the uptake of DSP-4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1994.62020697.x
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  • 5
    Electronic Resource
    Electronic Resource
    2-Phenylethylamine: A Modulator of Catecholamine Transmission in the Mammalian Central Nervous System? (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Since the identification of 2-phenylethylamine (β-phenylethylamine; PE) as a biogenic amine, there has been much discussion about what role, if any, it may have in the CNS. Indeed, the low endogenous concentration of PE in the brain and its relatively low potency in behavioral and pharmacological experiments have led some researchers to conclude that perhaps PE possessed no physiological role at all but that it was merely a metabolic by-product. Our findings have caused us to conclude otherwise, and in this article we review the neurochemical, neuropharmacological, and neurophysiological findings that lead us to propose that PE is a neuromodulator of catecholamine neurotransmission in the CNS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1990.tb05764.x
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of Deuterium Substitution on the Catabolism of β-Phenylethylamine: An In Vivo Study (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 46 (1986), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: β-Phenylethylamine (PE) hydrochloride injected intraperitoneally into rats was distributed evenly throughout the various regions of rat brain. Similarly, when a mixture of PE and α, α, β, β-deuterated PE ([2H4]PE) was injected, no regional differences were observed in the ratios of the amounts of [2H4]PE and PE present; however, significantly more [2H4]PE than PE was present, although a 1:1 mixture had been administered. Further experiments in which the amounts of [2H4]PE and PE in whole rat brain, liver, and plasma were quantified confirmed this finding. The maximum [2H4]PE-to-PE ratios observed were 67 in whole brain 1 h after injection and 8 in liver and in plasma 45 min after injection. The whole brain [2H4]PE-to-PE ratios were decreased by pargyline pretreatment. Subsequent experiments showed that more α, α-[2H4]PE than PE was present in whole brain, liver, and plasma of rats injected with an equimolar mixture of α, α-[2H4]PE and PE. In contrast, β, β-[2H4]PE was not enriched in comparison to PE under the same experimental conditions. We concluded that the basis for the enrichment of [2H4]PE and α, α-[2H4]PE compared to PE was due to protection of the deuterated analogs from the actions of monoamine oxidase and perhaps aldehyde dehydrogenase; this protection led to pronounced deuterium substitution effects in vivo especially in the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1986.tb12982.x
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  • 7
    Electronic Resource
    Electronic Resource
    Regulation of Aromatic l-Amino Acid Decarboxylase by Dopamine Receptors in the Rat Brain (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 58 (1992), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Decarboxylation of phenylalanine by aromatic l-amino acid decarboxylase (AADC) is the rate-limiting step in the synthesis of 2-phenylethylamine (PE), a putative modulator of dopamine transmission. Because neuroleptics increase the rate of accumulation of striatal PE, these studies were performed to determine whether this effect may be mediated by a change in AADC activity. Administration of the D1 antagonist SCH 23390 at doses of 0.01–1 mg/kg significantly increased rat striatal AADC activity in an in vitro assay (by 16–33%). Pimozide, a D2-receptor antagonist, when given at doses of 0.01–3 mg/kg, also increased AADC activity in the rat striatum (by 25–41%). In addition, pimozide at doses of 0.3 and 1 mg/kg increased AADC activity in the nucleus accumbens (by 33% and 45%) and at doses of 0.1, 0.3, and 1 mg/kg increased AADC activity in the olfactory tubercles (by 23%, 30%, and 28%, respectively). Analysis of the enzyme kinetics indicated that the Vmax increased with little change in the Km with l-3,4-dihydroxyphenylalanine as substrate. The AADC activity in the striatum showed a time-dependent response after the administration of SCH 23390 and pimozide: the activity was increased within 30 min and the increases lasted 2–4 h. Inhibition of protein synthesis by cycloheximide (10 mg/kg, 0.5 h) had no effect on the striatal AADC activity or on the increases in striatal AADC activity produced by pimozide or SCH 23390. The results indicate that the increases in AADC activity induced by dopamine-receptor blockers are not due to de novo synthesis of the enzyme. These results show that AADC activity in the striatum is regulated by D1 and D2 receptors and that the activities in the nucleus accumbens and olfactory tubercles are regulated by D2 receptors. The observation that dopamine-receptor antagonists stimulate the synthesis of PE may be explained by the increase in AADC activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb09765.x
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  • 8
    Electronic Resource
    Electronic Resource
    Changes in Levels of Dopamine and Tyramine in the Rat Caudate Nucleus Following Alterations of Impulse Flow in the Nigrostriatal Pathway (1983)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 40 (1983), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Following electrical stimulation of the substantia nigra for 1 h there was a substantial increase in dopamine (DA) turnover in the rat caudate nucleus evidenced by an increase in its acid metabolite homovanillic acid (HVA). Concurrently there was an increase in striatal m-tyramine (mTA) and a substantial decrease in p-tyramine (pTA). Lesioning the substantia nigra to decrease impulse flow resulted in a buildup of striatal DA and mTA, but again a decrease in pTA. Following pre-treatment with a tyrosine hydroxylase inhibitor, the effects of stimulation of the nigra on mTA were reversed, there being a significant decrease in this amine. The decrease of pTA in response was partially prevented by tyrosine hydroxylase inhibition. The effects of stimulation or substantia nigra lesions on pTA levels were reversed, however, by tyrosine hydroxylase inhibition, a significant increase in this amine being recorded. mTA and DA levels were largely unaffected by a combination of lesion and tyrosine hydroxylase inhibition. The results provide insight into the possible biosynthetic interrelationships between DA and the tyramine isomers in the rat caudate nucleus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1983.tb11295.x
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  • 9
    Electronic Resource
    Electronic Resource
    The Effect of Some Precursor Amino Acids and Enzyme Inhibitors on the Mouse Striatal Concentration of Tyramines and Homovanillic Acid (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The parenteral administration of L-phenylalanine or p-tyrosine increases the mouse striatal concentration of p-tyramine, an effect that is enhanced by monoamine oxidase inhibition and reduced by an L-aromatic aminoacid decarboxylase inhibitor. Striatal m-tyramine was increased following administration of L-phenylalanine or m-tyrosine and enhanced further by monoamine oxidase inhibition. It was also observed that m-tyrosine is a better substrate for decarboxylation than p-tyrosine, and that p-tyrosine decarboxylation was blocked by NSD 1055, while that of m-tyrosine was enhanced. The results obtained indicate that both isomers of tyramine are formed in the mouse striatum by hydroxylation of L-phenylalanine to p- or m-tyrosine followed by decarboxylation by a specific decarboxylase; an alternative pathway could be first the decarboxylation of phenylalanine to β-phenylethylamine, followed by its hydroxylation to p- or m-tyramine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1982.tb07971.x
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  • 10
    Electronic Resource
    Electronic Resource
    Estimation of the p and m Isomers of Hydroxyphenylacetic Acid in Mouse Brain by a Gas Chromatographic Procedure: Their Regional Distribution and the Effects of Some Drugs (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 37 (1982), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The mouse brain contains 12.5 and 4.1 ng/g of p- and m-hydroxyphenylacetic acids, respectively. The hydroxyphenylacetic acids were isolated by chromatography on DEAE-Sephadex A-25 and quantitated as their pentafluoropropionyl and hexafluoropropanol esters by use of a gas chromatograph equipped with an electron-capture detector. The highest concentrations of p- or m-hydroxyphenylacetic acids were observed in the caudate nuclei (27.9 and 8.7 ng/g, respectively) and olfactory tubercles (20.2 and 5.3 ng/g, respectively). The identities of the p- and m-hydroxyphenylacetic acids were further confirmed as a consequence of the reductions observed following monoamine oxidase inhibition or the increases observed in the appropriate acid following the parenteral administration of p- or m-tyramine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1982.tb12549.x
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