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1.
Large doses of L-dopa given to mice produced marked increases in brain dopamine, no change in norepinephrine, and a remarkable decrease in brain serotonin. This reduction apparently results from a release or displacement, or both, of serotonin from its storage sites.  相似文献   

2.
Treatment with the dopamine precursor L-dopa produced a significant accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in the caudate nucleus of the rat. In contrast, there was no change in the amount of cyclic AMP in the cerebellum. Accumulation of cyclic AMP in the caudate nucleus after administration of L-dopa was prevented by prior treatment with the decarboxylase inhibitor RO 4-4602. These observations and those in other laboratories support the assumption that dopamine formed from L-dopa selectively activates striatal adenylate cyclase. The in vivo activation of adenylate cyclase after treatment with L-dopa may be a useful model for studying neurological and psychiatric disorders that are thought to involve the dopaminergic system of the brain.  相似文献   

3.
Autoradiography combined with image analysis permitted quantitative visualization of dopamine (D2) and serotonin (S2) binding sites in rat brain. Forebrain sections were incubated with tritiated spiroperidol alone or with tritiated spiroperidol plus unlabeled compounds that saturated the D2 or S2 sites. By subtracting the digitized image of an autoradiograph derived from the latter sections from that of the former, the D2 or S2 sites were specifically revealed. The resulting quantitative images demonstrate the differing anatomical distributions of these sites. The D2 site is largely restricted to the striatal complex (caudate-putamen, nucleus accumbens septi, and olfactory tubercle), whereas the S2 site is enriched in layer 5 of motor cortex, the perirhinal and cingulate cortices, and the claustrum.  相似文献   

4.
The activity of L-dopa decarboxylase was greatly reduced in the striatum, less so in the hypothalamus, and unchanged in the cortex of brains of patients with Parkinson's disease. However, it appears that even in the striatum enough activity remained to allow for the formation of dopamine from L-dopa in patients treated with large doses of L-dopa.  相似文献   

5.
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   

6.
In organ cultures of intact rat pineal glands, N(6)O(2')-dibutyryl adenosine 3', 5'-monophosphate stimulates the conversion of tritiated trytophan to tritiated melatonin, as does L-norepinephrine. Potential sites of stimulation of melatonin production by dibutyryl cyclic adenosine monophosphate are discussed, based on observations that the dibutyryl analog also stimulates the conversion of serotonin labeled with carbon-14 to carbon-14-labeled melatonin without altering hydroxyin-dole-O-methyl transferase activity or intracellular accumulation of serotonin labeled with carbon-14.  相似文献   

7.
Primary cultures of astrocytes from neonatal rat brain were incubated with tritiated serotonin. After fixation they were stained by immunofluorescence for the astrocyte-specific marker glial fibrillary acidic protein and processed for autoradiography. Silver grain density was increased over cells positive for glial fibrillary acidic protein and was reduced to background levels when sodium was omitted from the medium or the specific inhibitors of serotonin uptake fluoxetine and chlorimipramine were present. The results indicate that mammalian astrocytes can take up serotonin by a sodium-dependent, high-affinity system previously thought to be the exclusive property of serotonergic nerve endings.  相似文献   

8.
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   

9.
Either L-dopa, in combination with 1-alpha-methyldopa hydrazine (MK-486), or 1-(2'-pyrimidyl)-4-piperonylpiperazine, an agent that stimulates dopamine receptors, relieves surgically induced tremor in monkeys and concomitantly evokes involuntary movements. These results indicate that tremor and involuntary movements are associated with a common mechanism and that the activity of the dopamine receptors is involved in the regulation of these dysfunctions.  相似文献   

10.
A syndrome of spontaneous orofacial dyskinesia was identified in groups of rats treated for 6 months with a wide range of neuroleptic drugs. Phenothiazines, thioxanthenes, and substituted benzamides were particularly likely to induce the syndrome. It was observed in the presence of a functional blockade of dopamine receptors and endured for at least 2.5 months after drug withdrawal. There was no relation between the syndrome and changes in striatal dopamine receptors, as indexed by the binding of tritiated spiperone and tritiated cis(Z)-flupenthixol. The syndrome parallels several of the features of clinical tardive dyskinesia, whose pathophysiology thus may not involve changes in the characteristics of striatal dopamine receptors.  相似文献   

11.
alpha-Methyl-3,4-dihydroxy-DLphenylalanine has been found to be an effective inhibitor of aromatic amino acid decarboxylation in man. This was shown by decreased formation of serotonin, tryptamine, and tyramine from the precursor amino acids. Reduction of amine biosynthesis is associated with lowering of blood pressure in hypertensive patients and a transient sedative effect.  相似文献   

12.
Adenosine receptors were made visible on light microscopy by autoradiography with tritiated cyclohexyladenosine. In the cerebellum, adenosine receptors were absent in Weaver mice, which lack granule cells, and were displaced in Reeler mice, which have displacements of granule cells. Thus, adenosine receptors appear to be located on the axon terminals of excitatory granule cells in the cerebellum. Removal of one eye of a rat depleted adenosine receptors in the contralateral superior colliculus, suggesting that the receptors occur on axon terminals of excitatory projections from retinal ganglion cells. The presence of adenosine receptors on excitatory axon terminals may explain synaptic inhibition by adenosine and the behavioral effects of xanthines.  相似文献   

13.
A soluble form of tryptophan-5-hydroxylase activity was found to be present in areas rich in serotonergic terminals (colliculi, hippocampus, septal area, and remaining telencephalon) as well as in brainstem, an area rich in cell bodies. The enzymatic activity in all brain regions, except the septal area, was inhibited to varying degrees following administration of parachlorophenylalanine. Destruction of the raphe nuclei in the midbrain led to a large and comparable decrease in both serotonin content and tryptophan hydroxylase activity of the hippocampus. In contrast, these lesions did not significantly affect the enzymatic activity of the septal area although the serotonin content was decreased by 72 percent. These findings suggest that the major portion of the tryptophan hydroxylase activity of the septal area is uniquely different from that found in other telencephalic areas in that it is not localized in serotonergic nerve terminals nor is it inhibited by parachlorophenylalanine.  相似文献   

14.
Transport of protein by goldfish optic nerve fibers   总被引:4,自引:0,他引:4  
After tritiated leucine was injected into the eye of goldfish, radio-active protein synthesized by the ganglion cell bodies moved down the optic axons at an average rate of 0.4 mm per day. Radioautograms of the optic tectum in which these axons end show that, as early as 24 hours after the injection, before the radioactivity in the tectal layer containing the optic axons had risen above background level, the layer containing the axon terminals was already heavily labeled. The radioactivity in the terminals reached a maximum about 48 hours after the injection and remained approximately constant for at least 23 days thereafter, whereas the radioactivity in the fiber layer increased significantly during the same interval, as the slowly moving protein component entered it. Thus there appears to be a special mechanism for rapid transport of protein from the cell body to the synaptic terminals, as well as a slower movement of protein down the axon.  相似文献   

15.
Movement disorders of aged rats: reversal by dopamine receptor stimulation   总被引:10,自引:0,他引:10  
When placed in a tank of water, aged rats (24 to 27 months old) showed marked impairments in swimming. Compared with young adult rats (3 to 4 months old), the older animals moved their limbs less vigorously and were less successful in keeping their heads above water. The young, but not old, rats maintained a position nearly horizontal to the water surface and planed across it. These movement dysfunctions of aged rats resemble those seen in young adult animals that have sustained injury to brain dopamine-containing neurons. The swimming impairments of the aged rats were reversed by the dopamine receptor stimulant apomorphine and by the biosynthetic precursor of dopamine, L-dopa. Thus, age-related alterations in brain dopaminergic systems may be responsible for some of the movement disturbances associated with senescence.  相似文献   

16.
The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy") is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.  相似文献   

17.
The subthalamic nucleus, a clinically important component of the extrapyramidal motor system, and a lateral area extending into the peduncle contain catecholamine terminals and dopamine receptors coupled to adenylate cyclase. In addition, dopamine agonists administered in vivo enhance glucose utilization in the region. Thus, neuronal function in this region is directly affected by dopamine and dopaminergic drugs.  相似文献   

18.
Cloning and expression of a cocaine-sensitive rat dopamine transporter   总被引:33,自引:0,他引:33  
The action of dopamine and other monoamine neurotransmitters at synapses is terminated predominantly by high-affinity reuptake into presynaptic terminals by specific sodium-dependent neurotransmitter transport proteins. A complementary DNA encoding a rat dopamine transporter has been isolated that exhibits high sequence similarity with the previously cloned norepinephrine and gamma-aminobutyric acid transporters. Transient expression of the complementary DNA in HeLa cells confirms the cocaine sensitivity of this transporter.  相似文献   

19.
The existence of cortical dopamine nerve terminals is demonstrated with a highly sensitive modification of the Falck-Hillarp fluorescence technique. This confirms previous biochemical reports of high dopamine levels in the cortex. The histochemistry reveals that the distribution is regional and confined to the limbic cortex.  相似文献   

20.
Erratum     
《Science (New York, N.Y.)》1978,200(4348):1370
In the report by L. D. Fetcher and Z. Annau [197, 680 (1977)], the values for whole brain dopamine levels in 1-day-old rats were given as 5.47 +/- 1.62 and 3.01 +/- 0.81, microg/g (wet weight) in air and CO subjects injected with L-dopa. The correct values are 5.47 +/- 0.38 and 3.01 +/- 0.20 microg/g. The difference between the groups is significant at P < .01 as reported.  相似文献   

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