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1.
Inhibition of biogenic amine uptake by hydrogen peroxide: a mechanism for toxic effects of 6-hydroxydopamine 总被引：2，自引：0，他引：2
Hydrogen peroxide, dialuric acid, or 6-hydroxydopamine inhibited the uptake of dopamine, norepinephrine, and serotonin into rat brain synaptosomal preparations. The addition of catalase protected all systems, but catalase was only partially protective for 6-hydroxydopamine acting upon catecholamine uptake. The data show that 6-hydroxydopamine generates hydrogen peroxide and that hydrogen peroxide can damage the biogenic amine uptake systems. Part of the damage caused by the 6-hydroxydopamine that accumulates in the catecholamine nerve terminals in vivo may be attributed to the hydrogen peroxide. 相似文献
2.
Dopamine synthesis: stimulation by a hypothalamic factor 总被引：2，自引：0，他引：2
The effect of treatment with the factor that inhibits the release of melanocyte stimulating hormone (MSH) identified as 1-prolyl-1-leucylglycinamide (MIF) on brain catecholamine synthesis was examined in normal and hypophysectomized rats. The tripeptide induced a dose-related increase in striatal dopamine synthesis in slices obtained from treated normal animals but not in hypophysectomized animals. Hypothalamic norepinephrine synthesis was unaltered by MIF treatment in normal as well as in hypophysectomized rats. In addition, dopamine and norepinephrine syntheses were depressed in untreated hypophysectomized animals, as compared to normal controls. These results constitute the first direct demonstration of a central neurochemical effect of a hypothalamic factor. 相似文献
3.
Recognition sites for the uptake of norepinephrine on adrenergic neurons in the brain and periphery were labeled with [3H]desipramine. The number of these uptake sites varied with the concentration of transmitter; depletion of norepinephrine with reserpine reduced the number of uptake sites, whereas increasing the concentration of norepinephrine induced by treatment with monoamine oxidase inhibitors raised the number of binding sites. These dynamic alterations in norepinephrine uptake recognition sites may regulate synaptic function homeostatically, providing less inactivation of reuptake when the synaptic concentration of the transmitter is low and increased inactivation when it is high. 相似文献
4.
Brains of rats undernourished from midgestation and killed at weaning contained 25 percent less norepinephrine than brains of adequately fed littermates. Perinatal undernutrition also suppressed the accumulation of brain dopamine. Paradoxically, the activity of tyrosine hydroxylase, the enzyme thought to be rate-limiting in catecholamine biosynthesis, was significantly increased in brains from undernourished animals. 相似文献
5.
Dopamine-accumulating retinal neurons revealed by in vitro fluorescence display a unique morphology 总被引：1，自引：0，他引：1
D M Dacey 《Science (New York, N.Y.)》1988,240(4856):1196-1198
Dopamine is the principal catecholamine neurotransmitter in the vertebrate retina. The shape of retinal neurons that accumulate dopamine has been demonstrated in an in vitro preparation of cat retina. This was achieved by the discovery that the combined uptake of dopamine and the indoleaminergic transmitter analog 5,7-dihydroxytryptamine leads to an intense, catecholamine-like fluorescence in the cell bodies and processes of presumed dopaminergic amacrine cells in the living retina. This fluorescence served as an in vitro marker for these cells, and their detailed morphology was analyzed after intracellular injection of horseradish peroxidase under direct microscopic control. The horseradish peroxidase-filled cells show an unprecedented neuronal morphology: each cell gives rise to multiple, axon-like processes that arise from, and extend for millimeters beyond, the dendritic tree. The unique structure of this type of amacrine cell suggests a function for dopamine in long-range lateral interactions in the inner plexiform layer. 相似文献
6.
The methoxy analogs of epinephrine, norepinephrine, and dopamine manifest some activity on smooth muscle and blood pressure. Metanephrine is as potent as epinephrine on rabbit aortic strips. The same compounds demonstrate a lesser potency on rabbit duodenum preparation, while 3-methoxy-dopamine produces a slight contraction of the duodenum. Both metanephrine and 3-methoxy-dopamine have 15 to 25 percent of the pressor activity of the original nonmethylated catecholamines. Normetanephrine is 1/600 as active as norepinephrine on the blood pressure of the cat. 相似文献
7.
A significant increase in shock-induced aggression occurs in the rat 4 days after an intraventricular injection of 90 micrograms of 6-hydroxydopa. Both fluorescent histology and biochemical assay demonstrate that brain norepinephrine is reduced by 90 micrograms of 6-hydroxydopa, while brain dopamine remains unaltered. This suggests that one form of aggressive behavior (shock-induced aggression) is modulated through a central noradrenergic system. 相似文献
8.
Proportional release of norepinephrine and dopamine- -hydroxylase from sympathetic nerves 总被引：13，自引：0，他引：13
R M Weinshilboum N B Thoa D G Johnson I J Kopin J Axelrod 《Science (New York, N.Y.)》1971,174(16):1349-1351
Dopamine-beta-hydroxylase(DBH), the enzyme that catalyzes the conversion of dopamine to norepinephrine, is localized in the vesicles containing catecholamine in sympathetic nerves. This enzyme is released with norepinephrine when the nerves to the guinea pig vas deferens are stimulated in vitro, and the amount of enzyme discharged increases as the length of stimulation periods increases. The amount of DBH released is proportional to the amount of norepinephrine released, and the ratio of norepinephrine to DBH discharged into the incubation medium is similar to that in the soluble portion of the contents of the synaptic vesicles from the vas deferens. These data are compatible with the release of the neurotransmitter norepinephrine and DBH from symnpathetic nerves by a process of exocytosis. 相似文献
9.
Cloning of a serotonin transporter affected by antidepressants 总被引：35，自引：0，他引：35
A complementary DNA clone for a serotonin (5HT) transporter has been isolated from rat basophilic leukemia cells. The complementary DNA sequence predicts a 653-amino acid protein with 12 to 13 putative transmembrane domains. The 5HT transporter has significant homology to the gamma-aminobutyric acid, dopamine, and norepinephrine transporters. Uptake by CV-1 cells expressing the transporter complementary DNA resembles 5HT uptake by platelets and brain synaptosomes; it is sensitive to antidepressants, amphetamine derivatives, and cocaine. 相似文献
10.
Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors 总被引：6，自引：0，他引：6
Dopamine, apomorphine, isoproterenol, and norepinephrine each increased the concentration of adenosine 3',5'-monophosphate in slice of rat caudate nucleus. The concentrations of dopamine, apomorphine isoproterenol, and norepinephrine causing half-maximal increases were 60, 150, 0.03 and 30 micromoles per liter, respectively. The effect of dopamine was blocked by fluphenazine, a dopamine receptor antagonist, but not by propranolol, a beta-andrenergic receptor antagonist. Conversely, the effect of isoproterenol was blocked by propranolol but not by fluphenazine. The results suggest that in rat caudate nucleus there are two distinct catecholamine receptors capable of causing increased concentrations of adenosine 3',5'-monophosphate, one having the characteristic of dopamine receptor, and the other having the characteristics of beta-adrenergic receptor. 相似文献
11.
The role of serotonin axons in modulating the norepinephrine neurotransmission system in rat brain was investigated. Selective lesions of the forebrain serotonergic system were made by injecting 5,7-dihydroxytryptamine into the midbrain raphe nuclei. Four to six weeks after the lesion, the uptake of 3H-labeled serotonin in the frontal cortex and the hippocampus was reduced by more than 90 percent, while neither the uptake of 3H-labeled norepinephrine nor the content of norepinephrine was affected in either tissue. The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions. Similarly, specific lesions of central serotonin axons produced by systemically administered p-chloramphetamine resulted in an increase in the binding of 3H-labeled dihydroalprenolol to beta-adrenergic receptors and in the production of adenosine 3',5'-monophosphate in response to isoproterenol. These results indicate that serotonin axons may regulate beta-adrenergic receptor number and function in brain. 相似文献
12.
Mice treated with 6-hydroxydopamine before they were chronically fed phenobarbital did not develop functional barbiturate tolerance, measured by duration of the loss of righting reflex and hypothermia. Injection of 6-hydroxydopamine caused significant depletion of brain norepinephrine, while brain dopamine levels were not significantly depleted. Intact brain noradrenergic systems seem to be necessary for developing tolerance to the hypnotic and hypothermic effects of the barbiturates. 相似文献
13.
D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons 总被引：63，自引：0，他引：63
C R Gerfen T M Engber L C Mahan Z Susel T N Chase F J Monsma D R Sibley 《Science (New York, N.Y.)》1990,250(4986):1429-1432
The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively. 相似文献
14.
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon 总被引：11，自引：0，他引：11
Explants of embryonic rat mesencephalon were grown in organotypic culture. Addition of 10 microM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the culture medium for 4 to 7 days resulted in loss of dopamine cell bodies and fiber outgrowths, as observed by fluorescence histochemistry. At the same time, the cultures showed decreased uptake of tritium-labeled dopamine. However, no signs of generalized toxicity were evident when the explant cultures were viewed by light and phase-contrast microscopy. These results show that MPTP exerts a relatively selective destructive action in dopamine neurons in vitro, similar to the action observed in humans and monkeys in vivo. Pargyline (10 microM), a monoamine oxidase inhibitor, protected the dopamine neurons in the explants. Organotypic cultures provide an experimental model for the study of the properties of MPTP in vitro. 相似文献
15.
Newborn rats that suckled mothers eating a diet containing 4 percent lead carbonate display hyperactivity, aggressiveness, and excessive stereotyped behavior starting at 4 weeks of age. There is an eightfold increase in the concentration of lead in brain, no change in norepinephrine, but a 20 percent decrease in dopamine relative to coetaneous controls. This suggests a relationship between central nervous system dysfunction due to lead and dopamine metabolism in brain. 相似文献
16.
By administering C(14)-la-beled tyrosine or H(3)-labeled 3,4-dihy-droxyphenylalanine to guinea pigs it has been possible to achieve sufficient labeling of the norepinephrine and dopamine in the brain to permit measurement of their turnover rates. The half-life of brain dopamine was about 2.5 hours. The half-life of norepinephrine was about 4 hours, suggesting a rate of synthesis of at least 0.03 to 0.04, microg/g per hr or 2.4 microg/day for the whole guinea pig brain. 相似文献
17.
Dopamine: mediator of brain polysome disaggregation after L-dopa 总被引：4，自引：0，他引：4
The disaggregation of brain polysomes which is produced by giving large doses of (L)-dopa to rats is not reproduced by administering its metabolite, 3-O-methyldopa, by giving D-dopa, which also depletes the brain of S-adenosylmethionine but is not converted to catecholamines, or by giving the L-dopa after a decarboxylase inhibitor. Polysome disaggregation is potentiated by the prior administration of a monoamine oxidase inhibitor, indicating that formation of a catecholamine is an obligatory requirement. These observations suggest that the mechanism by which L-dopa disaggregates brain polysomes involves its conversion to dopamine within the majority of brain cells. 相似文献
18.
D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects 总被引：15，自引：0，他引：15
J R Walters D A Bergstrom J H Carlson T N Chase A R Braun 《Science (New York, N.Y.)》1987,236(4802):719-722
D1 and D2 dopamine receptors exert synergistic effects on the firing rates of basal ganglia neurons and on the expression of stereotyped behavior in rats. Moreover, the ability of D2 agonists to induce changes in basal ganglia single unit activity and spontaneous motor activity is dependent upon the presence of endogenous dopamine to stimulate D1 receptors; in rats treated with alpha-methyl-rho-tyrosine to reduce endogenous dopamine levels, the neurophysiological and behavioral effects of the D2 agonist quinpirole are significantly attenuated, while the effects of nonselective agonists like apomorphine, which stimulate both D1 and D2 receptors, or combinations of a D2 agonist and a D1 agonist are not attenuated. Thus, the previously held view that D2 receptors alone are responsible for evoking the changes in behavior and basal ganglia output induced by nonselective dopamine agonists and endogenous dopamine is not supported by these results, which indicate that these phenomena require concurrent stimulation of both dopamine receptor subtypes. 相似文献
19.
Histochemical fluorescence after application of neurochemicals to caudate nucleus and septal area in vivo 总被引：1，自引：0，他引：1
The movement of carbachol, norepinephrine, and dopamine from cannula sites in caudate nucleus and septal area of freely moving rats was traced by means of biogenic amine fluorescence. Fluorescent patterns seen after application of carbachol and norepinephrine to brain tissue did not appear to differ from controls. Three types of movement from the cannula site after administration of dopamine were observed. There was a spherical distribution approximately 2 millimeters in diameter. Fluorescence also followed axonal pathways in the orthodromic direction, suggesting that dopamine may have been transported by " axonal streaming " or by some other unknown mechanism in periaxonal spaces. Because fluorescence was present in both the ependymal lining and the choroid plexus, it was inferred that the cerebral ventricles were also involved in the movement of chemical. Any attempt to ascribe anatomical localization to behavioral effects resulting from chemical stimulation of the brain should take into account the widespread movement of chemicals after their local application to brain tissue. 相似文献
20.
[目的]探讨罗布麻（Apocynum venetum L.）叶总黄酮提物抗抑郁作用的机理。[方法]采用大鼠慢性应激抑郁模型,利用液相色谱-质谱串联法测定大鼠脑内单胺类神经递质[去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）]的含量。[结果]慢性应激抑郁组动物组织内DA、5-HT和NE含量与正常组相比均极显著降低（P〈0.01）。罗布麻总叶黄酮提取物处理组大鼠脑中DA和NE含量与慢性应激抑郁组相比显著或极显著上升,且随着剂量的增大,这种作用更加明显;70.0 mg/kg罗布麻叶黄酮提取物处理与盐酸氟西汀（3.5mg/kg）效果一致;但罗布麻叶总黄酮提取物处理组大鼠脑中5-HT含量与慢性应激抑郁组相比没有明显变化,阳性对照药氟西汀显著增加了抑郁大鼠脑组织中DA、NE和5-HT含量。[结论]该研究证实了抑郁症发病的神经递质假说,同时发现罗布麻叶可以逆转抑郁大鼠脑内单胺类物质NE、DA含量的降低,这也可能是其抗抑郁作用的机理之一。 相似文献