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141.
A Closer Look at Amphetamine-Induced Reverse Transport and Trafficking of the Dopamine and Norepinephrine Transporters 总被引:1,自引:0,他引:1
Amphetamine (AMPH) and its derivatives are regularly used in the treatment of a wide array of disorders such as attention-deficit
hyperactivity disorder (ADHD), obesity, traumatic brain injury, and narcolepsy (Prog Neurobiol 75:406–433, 2005; J Am Med Assoc 105:2051–2054, 1935; J Am Acad Child Adolesc Psychiatry 41:514–521, 2002; Neuron 43:261–269, 2004; Annu Rev Pharmacol Toxicol 47:681–698, 2007; Drugs Aging 21:67–79, 2004). Despite the important medicinal role for AMPH, it is more widely known for its psychostimulant and addictive properties
as a drug of abuse. The primary molecular targets of AMPH are both the vesicular monoamine transporters (VMATs) and plasma
membrane monoamine—dopamine (DA), norepinephrine (NE), and serotonin (5-HT)—transporters. The rewarding and addicting properties
of AMPH rely on its ability to act as a substrate for these transporters and ultimately increase extracellular levels of monoamines.
AMPH achieves this elevation in extracellular levels of neurotransmitter by inducing synaptic vesicle depletion, which increases
intracellular monoamine levels, and also by promoting reverse transport (efflux) through plasma membrane monoamine transporters
(J Biol Chem 237:2311–2317, 1962; Med Exp Int J Exp Med 6:47–53, 1962; Neuron 19:1271–1283, 1997; J Physiol 144:314–336, 1958; J Neurosci 18:1979–1986, 1998; Science 237:1219–1223, 1987; J Neurosc 15:4102–4108, 1995). This review will focus on two important aspects of AMPH-induced regulation of the plasma membrane monoamine transporters—transporter
mediated monoamine efflux and transporter trafficking. 相似文献
142.
Involvement of Hydrogen Peroxide Generated by Polyamine Oxidative Degradation in the Development of Lateral Roots in Soybean 总被引:3,自引:0,他引:3
Guo-Xing Su Wen-Hua Zhang You-Liang Liu 《植物学报(英文版)》2006,48(4):426-432
In order to determine whether hydrogen peroxide (H2O2) generated by polyamlne oxidative degradation Is Involved In the development of lateral roots In soybean, the length and the number of lateral roots, the actlvltlea of polyamlne oxldases and dlamlne oxldases, and the endogenous free polyamlne and H2O2 content were analyzed In soybean (Giycine max (Linn.) Merr.) main roots of 2-d-old seedlings after treatments for 2 d with exogenous β-hydroxyethylhydrazine (an Inhibitor of polyamlne oxldases), H202, putresclne, cyclohexylamlne (an Inhibitor of spermidine synthase) or N,N'-dimethylthlourea (a scavenger of hydrogen peroxide).β-hydroxyethylhydrazlne treatment strongly Inhibited the development of lateral roots In soybean seedlings, reduced the activities of polyamine oxldases and dlamlne oxidases, decreased H2O2 levels, and led to the accumulation of endogenous polyamlnes In the main roots. The inhibitory effect of β-hydroxyethylhydrazlne on root development could be alleviated by exogenously applied 10 μmol/L H2O2 (a major product of polyamlne oxidation). Treatment with cyclohexylamlne and putresclne promoted root growth slightly, but treatment with cyclohexylamlne plus N,N'dlmethylthlourea or putresclne plus N,N'-dlmethylthlourea prevented the development of soybean lateral roots. The effects of these treatments on the development of soybean lateral roots were consistent with the changes In endogenous H2O2 levels. These results suggest that the development of soybean lateral roots Is associated with the oxidative degradation of polyamlnes, and that their products, especially H2O2, are likely to play an Important role In the growth of soybean lateral roots. 相似文献
143.
A comparative study of the expression of monoamine oxidase-A and -B mRNA and protein in non-CNS human tissues 总被引:2,自引:0,他引:2
Sivasubramaniam SD Finch CC Rodriguez MJ Mahy N Billett EE 《Cell and tissue research》2003,313(3):291-300
The distributions of monoamine oxidase (MAO)-A and -B proteins and mRNAs in human heart, lung, liver, duodenum, kidney and vasculature were compared using immunohistochemistry and cRNA in situ hybridisation. MAO-A and -B mRNA were detected in all tissues, to differing extents, but particularly in glomeruli, hepatocytes, and the crypts, muscularis mucosa and muscularis externa of duodenum. Renal proximal and distal tubules and loops of Henle had more intense labelling for mRNA of MAO-B than MAO-A; this was reflected in MAO protein expression. Little immunoreactivity was detected in glomeruli. Hepatocytes expressed MAO-A moderately, but MAO-B strongly. In lungs, similar moderately intense labelling for both MAO mRNAs and immunoreactivities was evident in pneumocytes, and epithelial and smooth muscle cells. Cardiomyocytes contained both MAO isoforms, but with more, albeit moderate, labelling for MAO-A. Both isoforms were expressed equally in duodenal villi, crypts, muscularis externa and mucosa; lower level expression occurred in mucosal and submucosal cells. MAO-A and -B mRNA were detected in endothelia, adventitia and media of a renal interlobular artery, but protein immunoreactivities were chiefly in the adventitia. The data reveal widespread tissue distribution of MAO mRNAs and proteins, but indicate that presence of MAO mRNAs does not invariably reflect quantitatively its protein expression. 相似文献
144.
Peroxidases (EC 1.11.1.7) from hypocotyls of Lupinus albus L. cv. Rio Maior have been characterised using one- and two-dimensional, native electrophoretic techniques. Data are presented showing the complexity in charge and molecular size or shape of these peroxidases. We report the finding of a new acidic peroxidase and several new basic peroxidases in these hypocotyls, and of their stability to treatments considered to break ligand-induced variants and conformational variants derived from differences in polypeptide folding. Densitometric data demonstrate that these new peroxidases contribute up to 60 of the total peroxidase activity in hypocotyls. Studies of intercellular fluid, cell-wall and soluble fractions, with assays of purity were conducted in an attempt to define the subcellular locations of these additional peroxidases. The acidic form (pI 4.1) is greatly enriched in soluble fractions, three of the basic peroxidases (pIs 9.5, 9.7 and >9.7) are strongly associated to the cell wall, ad a minor, basic component (pI 9.7) is enriched in the intercellular fluid. Individual peroxidase activities with the substrates coniferyl alcohol, ferulic acid or indole acetic acid were compared by densitometric analysis of zymograms with those for guaiacol, and notable differences between these peroxidases in their capacity to oxidise indole acetic acid in vitro were identified. The possible functions of these peroxidases in vivo and their implications to current understanding of peroxidases in L. albus are discussed.Abbreviations APAGE
anionic polyacrylamide gel electrophoresis
- CA
coniferyl alcohol
- CPAGE
cationic polyacrylamide gel electrophoresis
- IEF
isoelectric focusin
- NEIEF
non-equilibrated isoelectric focusing
- 2D
two dimensional
- pI
isoelectric point
- RCPAGE
reversed current polyacrylamide gel electrophoresis 相似文献
145.
Abstract: In the postmortem human brain (27 specimens of frontal cortex, Brodmann area 9), the specific binding of the antagonists [3H]RX 821002 (2-methoxyidazoxan) to α2A-adrenoceptors and that of [3H]idazoxan to l2-imidazo-line sites (a nonadrenoceptor mitochondrial site) were determined in parallel to study the effect of aging (range, 4–89 years) on both brain proteins. The density of α2A-adrenoceptors and age were negatively correlated (r=-0.71; p < 0.001). In contrast, the density of l2-imidazo-line sites was positively correlated with aging (r= 0.59; p < 0.005). The ratio of receptor densities (α2A/l2) also showed a marked negative correlation with age (r=-0.76; p < 0.001). In an age-selected group (range, 10–89 years), the density of monoamine oxidase (MAO)-B sites labeled by [3H]Ro 19–6327 (lazabemide) also showed a positive correlation with age (r= 0.80; p < 0.005). In these subjects, the density of l2-imidazoline sites correlated well with the density of MAO-B sites (r= 0.70; p < 0.005). The ratio of the density of these sites (MAO-B/l2) did not correlate with the age of the subject at death (r=-0.15). In the human frontal cortex, idazoxan displayed very low affinity (Ki= 89 μM) against the binding of [3H]Ro 19–6327 to MAO-B, which discounted a direct interaction of [3H]idazoxan with the active center of the enzyme and indicated that the l2-imidazoline site cannot be identified with MAO-B. However, l2-imidazoline sites and MAO-B show a clear coexpression not only in the human frontal cortex during the process of aging, but also in various brain regions of the human and rat brains. It is suggested that the l2-imidazoline site has a specific location on glial (astrocyte) cells. 相似文献
146.
The Deduced Amino Acid Sequences of Human Platelet and Frontal Cortex Monoamine Oxidase B Are Identical 总被引:6,自引:0,他引:6
Abstract: Monoamine oxidases (MAOs) A and B play important roles in the metabolism of neuroactive, vasoactive amines. Human platelets contain only MAO B, often used as an indicator of brain MAO B. The validity of this model remained to be evaluated. This report describes the molecular cloning of human MAO B from frontal cortex and platelets. Two overlapping PCR-amplified clones of human platelet MAO B and four PCR-amplified clones of human frontal cortex MAO B covering the entire coding region were sequenced using five internal oligomers and M13 reverse and forward primers. The nucleotide sequences of human MAO B cDNA from platelet and frontal cortex were identical to that of human liver MAO B except for three nucleotides that differed in frontal cortex: nucleotides 440 A → G, 794 C → T, and 825 C → T. Whether or not these differences are artifactual, all three represent silent mutations, which would not alter the amino acid of the encoded polypeptides. Thus, the deduced amino acid sequences of MAO B from frontal cortex, platelet, and liver are identical. These findings indicate the validity of using platelet MAO B mRNA as a marker for brain MAO B and provide a new approach to study the role of brain MAO B in humans. 相似文献
147.
The degree of relatedness among mammalian xanthine oxidases (XO) was determined by microcomplement fixation. Rabbit anti bovine milk XO serum was tested against xanthine oxidase (homologous protein) and against the heterologous proteins of bovine liver, monkey liver, rat liver, lactating cow serum, nonlactating cow serum, and steer serum. The indices of dissimilarity for the heterologous proteins were expressed as units of immunological distance and the percent sequence differences among these proteins inferred from the y=5x relationship where y is immunological distance and x is percent sequence difference. Rat liver XO differed by approximately 27% in amino acid sequence from bovine milk XO. In order of increasing immunological distance from bovine milk XO, the sources of XO ranked as follows: lactating cow serum < nonlactating cow serum < steer serum = beef liver < monkey liver < rat liver. The monkey ranked much closer than the rat in order of phylogenetic kinship to the cow. Starch gel electrophoresis of liver, milk, and serum showed that the milk and the serum contained only cationic forms of xanthine oxidase while all the liver samples tested contained cationic as well as anionic forms of the enzyme. The electrophoretic mobility properties of xanthine oxidase confirmed the polymorphic nature of the enzyme as revealed by the immunological data.This investigation was supported by the National Dairy Council, Chicago, Illinois, and by USPHS Grant AM16726. 相似文献
148.
For the low molecular weight laccases II and III of Podospora anserina the kinetic parameters Michaelis constant (K
M) and maximum reaction velocity (V) were determined polarographically under pH optimum conditions for representative substrates of different substitution patterns.Laccase II showed two peaks in its pH optimum curve, each with a different substrate specificity, indicating structural differences to laccase III which exhibits only one broad peak.Under optimum conditions the affinities of various substrates are determined by their substitution patterns: high affinity for simple o-and p-diphenols, low affinity for m-phenols. The maximal velocity remains largely uninfluenced.This study of the effect of substitution on substrate utilization leads to the assumption that there is no specific reactive site for m-phenols in either laccase. Oxidation of m-phenols, however, takes only place at high pH values. 相似文献
149.
Summary The reaction of nerve endings in the median eminence of the rat to zinc iodide-osmium tetroxide (ZIO) staining was examined electron microscopically under normal and experimental conditions. The experimental condition of catecholamine exhaustion in the nerve endings was induced by the administration of H44/68 and reserpine. Vesicles in the terminals of catecholaminergic nerves reacted similarly to ZIO staining in both normal and experimental material. The majority of synaptic vesicles in various terminals gave a positive ZIO reaction. The neurosecretory elementary granules, however, failed to react with ZIO. On the other hand, some nerve terminals in the external layer of the median eminence showed a strong positive reaction in the cytoplasmic matrix, in mitochondria as well as in synaptic vesicles. These findings strongly suggest that the ZIO-positive substance in nerve terminals is not the transmitter itself, i.e. the monoamine, but rather represents a range of substances commonly found in various kinds of synaptic vesicles and is probably proteinaceous in nature. A brief discussion is also given on the difference in ZIO reactivity between neurosecretory elementary granules and small vesicles in the hypothalamo-hypophyseal tract.This work was supported in part by a research grant from the Ministry of Education, Japan 相似文献
150.