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1.
Brain serotonin cocentrations at 1 p.m. were significantly elevated 1 hour after rats received a dose of L-tryptophan (12.5 milligrams per kilogram. intraperitoneally) smaller than one-twentieth of the normal daily dietary intake. Plasma and brain tryptophan levels were elevated 10 to 60 minutes after the injection, but they never exceeded the concentrationis that occur nocturnally in untreated aninmals as result of their normal 24-hour rhythms. These data suggest that physiological changes in plasma tryptophan concentration influenice brain serotonin levels. 相似文献
2.
Narcotic tolerance and dependence: lack of relationship with serotonin turnover in the brain 总被引：1，自引：0，他引：1
Serotonin turnover was measured in mouse brain by means of the conversion of radioactivity from labeled tryptophan into serotonin. Animals with a high degree of tolerance to and physical dependence on morphine did not differ from control mice. 相似文献
3.
The effects of short- and long-term administration of morphine on the activity of two measurable forms of rat brain tryptophan hydroxylase were studied. Morphine administration produced an immediate decrease and a longterm increase in the nerve ending (particulate) enzyme activity but did not change the cell body (soluble) enzyme activity. Cocaine administration demnonstrated a short-term decrcease in measurable nerve eniding enzyme activity that was due to the inhibition of the high affinity uptake (the Michaelis constant, K(m) is 10-(5) molar) of trytophan, the serotonin precursor. Cocaine did not aflect the low affinity uptake K(m) = 10-(5) molar) of tryptophan. Both the uptake of the precursor and the enizymiie activity appeared to be drug-sensitive regullatory processes in the biosynthlesis of serotonin. 相似文献
4.
The histochemical fluorescence of those neurons in brainstem raphe nuclei which are presumed to contain serotonin is selectively and stereospecifically enhanced by L-tryptophan at doses that also produce an elevation in the concentration of serotonin. However, contrary to our assumptions, the increase in raphe fluorescence is not prevented by p-chlorophenylalanine, an inhibitor of serotonin synthesis. These results suggest that under some conditions derivatives of tryptophan other than, or in addition to, serotonin may be of significance in raphe neurons. 相似文献
5.
Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated. 相似文献
6.
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
7.
Cyclic adenosine monophosphate: stimulation of melatonin and serotonin synthesis in cultured rat pineals 总被引：3，自引：0，他引：3
Dibutyryl cyclic adenosine monophosphate, like norepinephrine, stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture. Unlike norepinephrine, dibutyryl cyclic adenosine monophosphate does not enhance the accumulation of labeled tryptophan or protein within the pineal. These findings are compatible with the hypothesis that cyclic adenosine monophosphate mediates some, but not all, of the effects of norepinephrine. 相似文献
8.
Some neurons of the rat central nervous system contain aromatic-L-amino-acid decarboxylase but not monoamines 总被引：7，自引：0，他引：7
C B Jaeger G Teitelman T H Joh V R Albert D H Park D J Reis 《Science (New York, N.Y.)》1983,219(4589):1233-1235
Neurons containing the enzyme aromatic-L-amino-acid decarboxylase (AADC) but lacking either tyrosine hydroxylase or serotonin were found in the spinal cord of neonatal and adult rats by light and electron microscopic immunocytochemistry. The majority of these neurons localized to area X of Rexed contact ependyma. Thus, spinal AADC neurons have the enzymatic capacity to catalyze directly the conversion of the amino acids tyrosine, tryptophan, or phenylalanine to their respective amines tyramine, tryptamine, or phenylethylamine. These amines normally present in the central nervous system may be of potential clinical significance as endogenous psychotomimetics. 相似文献
9.
Persistent increase in brain serotonin turnover after chronic administration of LSD in the rat 总被引：1，自引：0，他引：1
Lysergic acid diethylamide at doses of 20 micrograms per kilogram per day was administered orally to rats for I month. Eighteen hours after the final dose a 25 to 30 percent increase in the synthesis and turnover of serotonin was noted, as well as a moderate but significant increase in the concentration of tryptophan (18 percent) and serotonin (13 percent) in the brain. 相似文献
10.
One hour after administration of L-dopa (50 to 300 milligrams per kilogram), there is a marked disaggregation of brain polysomes in immature rats. Adult animals show a similar response, but require larger doses of the amino acid (500 milligrams per kilogram). Single doses of L-dopa significantly elevate amounts of tryptophan in the brain; hence their effect on polysomes does not result from the unavailability of this amino acid. 相似文献
11.
Reserpine, when administered to animals stressed by exposure to cold, does not induce sedation or appreciably lower brain serotonin, but markedly lowers brain norepinephrine. Reserpine in cold-exposed hypophysectomized rats elicits sedation and releases both amines equally. The results support the view that the tranquilizing action of reserpine is not related to brain norepinephrine loss but rather to change in the level of brain serotonin. 相似文献
12.
Short- and long-term lithium administration: effects on the brain's serotonergic biosynthetic systems 总被引：4，自引：0，他引：4
Short-term treatment with lithium chloride stimulates the uptake of tryptophan and its conversion to serotonin by striate synaptosomes. Preincubation of striate synaptosomes with L-tryptophan and in vivo administration of L-tryptophan appear to act in a similar manner. Midbrain tryptophan hydroxylase activity is reduced in temporal continuity with the lithium-induced activation of tryptophan uptake and conversion. By 10 days, conversion of tryptophan to serotonin in nerve endings becomes a joint function of the maintained increased uptake of tryptophan and a decreased level of tryptophan hydroxylase activity in nerve endings. The occurrence of this delayed alteration corresponds in time to the previously described axoplasmic flow rate for tryptophan hydroxylase. 相似文献
13.
Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis 总被引：21，自引：0，他引：21
In rats after portacaval anastomosis (an animal model of chronic liver disease), transport of tryptophan and other members of the large neutral amino acid group from blood to brain was markedly enhanced. Increased transport activity was apparently restricted to the neutral amino acid transport system, since brain uptake of glucose, inulin, and tyramine was unaffected while blood-brain arginine transport was significantly reduced. These results strikingly confirm the hypothesis that carrier-mediated blood-brain transport is the limiting factor determining the availability of the neutral amino acids to the brain. The encephalopathy associated with cirrhosis may be the result of abnormal neurotransmitter metabolism and neurotransmission secondary to increased neutral amino acid transport activity and an increased brain content of members of the neutral amino acid group. 相似文献
14.
Lesurtel M Graf R Aleil B Walther DJ Tian Y Jochum W Gachet C Bader M Clavien PA 《Science (New York, N.Y.)》2006,312(5770):104-107
The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration. 相似文献
15.
Tryptophan deficiency in rabbit reticulocytes: polyribosomes during interrupted growth of hemoglobin chains 总被引：9，自引：0，他引：9
Of several amino acids essential for optimum hemoglobin synthesis by the rabbit reticulocyte, only omission of tryptophan results in polyribosome disaggregation. This disaggregation is prevented by the omission of both tryptophan and an amino acid that is relatively more essential than tryptophan for hemoglobin synthesis. Since tryptophan is located only near the amino-terminal ends of both chains of rabbit globin, the results indicate that single ribosomes and those in polyribosomes are in a dynamic state in the intact cell. 相似文献
16.
Protein synthesis in rat liver: influence of amino acids in diet on microsomes and polysomes 总被引：19，自引：0，他引：19
Rats were killed 1 hour after having been fed by stomach tube with amino acid mixtures that were either nutritionally complete or lacked tryptophan. Microsomes isolated from the livers of animals fed the incomplete mixture showed a reduced capacity to incorporate (14)C-leucine in vitro, and polysomes prepared from the same livers showed an increased proportion of monosomes and disomes. Prior treatment with actinomycin D did not prevent these differences in response to the two amino acid mixtures, an indication that synthesis of messenger RNA may not be involved in the cell mechanism which recognizes differences in amino acid pattern. 相似文献
17.
Although amino acid auxotrophs are among the most frequently isolated mutations in microorganisms, no mutants that require amino acids have been isolated at the whole plant level. Tryptophan-requiring mutants of the cruciferous plant Arabidopsis thaliana have now been isolated by selecting for resistance to 5-methylanthranilic acid. The tryptophan requirement of one mutant, trpl-1, results from a defect in the second step of the tryptophan pathway catalyzed by anthranilate phosphoribosyl transferase. Mutant trpl-1 plants are highly fluorescent and aromatic because they accumulate anthranilic acid and anthranilate beta-glucoside. Plants homozygous for the trpl-1 mutation exhibit a syndrome of morphological defects suggestive of a defect in the biosynthesis, metabolism, or localization of a tryptophan derivative such as auxin. All of these morphological phenotypes cosegregate with the tryptophan requirement as a simple Mendelian recessive trait. 相似文献
18.
Ricaurte GA Yuan J Hatzidimitriou G Cord BJ McCann UD 《Science (New York, N.Y.)》2002,297(5590):2260-2263
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
19.
It has been found that the sulfonamide bond is relatively susceptible to photolytic cleavage. The breakdown was effected either by irradiation with a source having a continuous emission above the wavelengths of 1800 angstroms or by another source emitting principally at 2537 angstroms. Less destruction of the amino acids was seen with the latter relative to the sulfonamide bond cleavage. The cleavage was not effected by irradiation at wavelengths greater than about 3000 angstroms. Side reactions were noted involving decarboxylation, demination, and destruction of certain susceptible amino acids such as tryptophan. In only one case was a product found that arose from cleavage of a carboxamide bond; glycyltyrosine gave glycine and tyrosine upon irradiation. A yield of 75 percent of the corresponding amino acid has been obtained by irradiation of tosylhistidine; yields of 75 to 100 percent have been obtained from sulfamic acid (NH(2)SO(3)H). A qualitative method for identifying sulfonylated amino acids is described. 相似文献
20.
Characterization of "peak E," a novel amino acid associated with eosinophilia-myalgia syndrome 总被引：4，自引：0，他引：4
A N Mayeno F Lin C S Foote D A Loegering M M Ames C W Hedberg G J Gleich 《Science (New York, N.Y.)》1990,250(4988):1707-1708
Epidemiologic studies strongly associate eosinophilia-myalgia syndrome (EMS) with ingestion of tryptophan containing a contaminant ("peak E"). Prior reports have suggested that peak E is the di-tryptophan N alpha-animal of acetaldehyde. Spectral and chemical studies now demonstrate that peak E is 1,1'-ethylidenebis[tryptophan]. This novel amino acid may be the etiological agent responsible for EMS, or it may be a marker of a still unidentified causal agent. 相似文献