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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extended theory about a dysfunction of the serotoninergic system in depression and schizophrenia includes the hypothesis of a disturbance in the transport systems of tryptophan and tyrosine from blood to brain. It would be interesting to know if blood cells may be used as a model for the central transport mechanisms of these amino acids. After an oral load, the in vivo distribution of L-tryptophan (50 mg/kg) was studied in the blood plasma, in the different blood cells and its binding to plasma albumin, in six healthy, seven schizophrenic and two depressive subjects. In all the compartments studied, tryptophan reached a peak, 1--2 hours after the load. Before and after the load, the variation of the tryptophan concentration in the erythrocytes was parallel to the plasma free tryptophan, whereas the uptake of this amino acid was higher in leukocytes and thrombocytes than in erythrocytes. However, this model does not show differences between schizophrenic and normal subjects with regard to the transport of tryptophan and tyrosine in these cells.
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PMID:Distribution of tryptophan in erythrocytes, leukocytes and thrombocytes, and its binding to plasma albumin. 29 Jul 55

As requirements for tryptophan for synthesis of protein and 5-hydroxytryptamine were comparable in rat brain, during depletion of tryptophan there could be competition between the two pathways for the amino acid. This implied that tryptophan should be rate-limiting for protein synthesis and this was found in the short term when concentrations of the amino acid were reduced in rats. Multicompartmental studies of tryptophan and tyrosine in controls and patients subject to unipolar depression defined two main pools of the amino acid provisionally assigned to extracellular and intracellular spaces. For tyrosine, mean values for the extracellular space were comparable to those of controls. The concentration of tyrosine was low in the intracellular space in both depressed and recovered patients, but the raised fractional clearance rates for this compartment during depression had returned to normal on remission. Plasma tryptophan concentrations were significantly reduced in depression with intermediate values after recovery. This suggested that the procedure used may have been mildly stressful and that this had evoked an idiosyncratic response to the stress in the depressed patients, which was characterized by inability to maintain concentrations of this amino acid in plasma. The findings for both amino acids may have a bearing on the aetiology of unipolar affective disorder.
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PMID:Distribution of tryptophan and tyrosine in unipolar affective disorders as defined by multicompartmental analysis. 29 Jul 58

Cerebral ischemia was induced in normothermic, artificially ventilated rats, anesthetized with 70% N2O or 150 mg/kg of phenobarbitone, by bilateral occlusion of the common carotid arteries and by simultaneous depression of the mean arterial blood pressure to 50 mm Hg. The levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 15 min of ischemia as well as after 30 min of recirculation. In separate experiments (70% N2O) the rate of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) was determined in three different brain regions (striatum, limbic forebrain and hemispheres) during recirculation. During ischemia, the monoamine pattern was unaffected. Following recirculation, increases in DA, 5-HIAA, tyrosine and tryptophan were found irrespective of the type of anesthesia used. Pronounced postischemic decreases in NA and 5-HT were observed in animals anesthetized with nitrous oxide but not in those given phenobarbitone. During recirculation the rate of tyrosine hydroxylation increased in all three brain regions while tryptophan hydroxylation was reduced. It is tentatively concluded that following transient, global cerebral ischemia, neuronal activity is low or eliminated in dopaminergic and serotoninergic neurons and high in noradrenergic neurons.
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PMID:Influence of transient ischemia on monoamine metabolism in the rat brain during nitrous oxide and phenobarbitone anaesthesia. 30 81

Repetitive stimulation of the locus coeruleus evoked strong inhibition of the firing rate of about 50% of cells of the cingulate rat cortex. Forty per cent of the cells were not affected and 9% were excited by stimulation of the locus coeruleus. Pretreatment of the rats with reserpine and alpha-methyl-p-tyrosine drastically reduced the percentage of cells inhibited by locus coeruleus stimulation. The cells inhibited in response to stimulation of the locus coeruleus as well as those not inhibited were depressed by microiontophoretically applied norepinephrine. This inhibitory action of NE was observed in rats anesthetized either with urethane, chloral hydrate or with Nembutal. The transsynaptically elicited, as well as the norepinephrine elicited, depression of the cells' discharge rate was antagonized by the microiontophoretically applied beta-receptor blocking drug MJ 1999. These data suggest that the inhibitory action on cingulate cortical cells of locus coeruleus stimulation is mediated by the dorsal ascending noradrenergic pathway.
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PMID:Activation of an inhibitory noradrenergic pathway projecting from the locus coeruleus to the cingulate cortex of the rat. 69 22

Several recent data indicate the blood-brain transport of amino acids as a critical factor in the synthesis of monoamines. The complex, peripheral and central regulation of TP transport plays an essential role sine TP-hydroxylase is not a saturated enzyme. The hydroxylated derivatives 5-HTP and dopa are probably transported into the brain by similar mechanisms as their precursors TP and tyrosine, respectively. The maic-depressive patients show an increased uptake of administered L-5-HTP in the depressive phase, whereas L-dopa uptake is enhanced in the manic phase. Heuristically, we propose a biochemical model of manic-depressive psychosis in which an increased TP uptake causes alternation in the balance of monoaminergic system activity. Depression is possibly characterized by a hyperserotonergic and a relative hypocatecholaminergic activity. In contrast, mania is possibly determined by a hypercatecholaminergic (NA and DA) and a relative hyposerotonergic activity. The data offered by the physiology of monoamines, the semeiology and the biological alterations of the manic-depressive psychosis, as well as the monoaminergic and the electrolyte theory of manic-depressive psychosis. A diminution of the transport of TP with consequent increase of that of tyrosine represents a possible biochemical model of schizophrenia which may be well explained by a hyposerotonergic-hyperdopaminergic activity, with or without noradrenergic insufficiency. This model is compatible with our knowledge on the monoamine physiology, the biological alterations of schizophrenia, the therapeutical results as well as with the classical clinical notions (typology, intermediate syndromes and crossed heritance).
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PMID:The common pathophysiology of monaminergic psychoses: a new hypothesis. 77 59

6-Thioguanine, at a dose of 40 mg/kg body weight, was administered to rats at 12 hr after partial hepatectomy; 6 hr later, liver polysomes and cell sap were isolated and utilized to measure the effects of this antimetabolite on protein synthesis in vitro. When radioactive leucine was used to label peptides synthesized in vitro, no difference was observed between polyacrylamide gradient gel scans of systems derived from control regenerating liver and those from 6-thioguanine-treated regenerating liver. However, when radioactive tyrosine was used as the tracer to monitor synthesized peptides, a depression in the 30,000-molecular weight region of scans of products synthesized in systems derived from 6-thioguanine-treated regenerating liver was observed. Recombination experiments showed this effect to be due to the polysome component of the system. When equal amounts of polyadenylic acid-containing RNA from 6-thioguanine-treated or control regenerating liver were added to a wheat germ in vitro protein-synthesizing system, polyacrylamide gel scans of the products synthesized in the presence of radioactive tyrosine showed that more peptides were synthesized from polyadenylic acid-containing RNA from 6-thioguanine-treated rats than from control polyadenylic acid-containing RNA. That this phenomenon might be the result of incorporation of the analog into RNA was shown by the finding that all types of RNA containing 6-thioguainine, with the greatest concentration occurring in polyadenylic acid-containing RNA.
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PMID:Effects of 6-thioguanine on RNA biosynthesis in regenerating rat liver. 85 43

The mechanism of action of a carboxypeptidase inhibitor from potatoes has been probed by studying its interaction with derivatives of carboxypeptidase A containing modified residues at the active site. Arsanilazocarboxypeptidase A, a derivative containing a chromophore attached to tyrosine 248, exhibits a circular dichroism spectrum which is sensitive to the presence of ligands at the active site (Kagan, H.M., and Vallee, B.L. (1969), Biochemistry 8, 4223). Since the spectral change attending binding of the carboxypeptidase inhibitor to arsanilazocarboxypeptidase A is similar to that produced by small substrates and inhibitors, the enzyme-inhibitor interaction also involves the enzyme active site. Catalytic activity is not required for inhibitor binding. Complexes of the inhibitor with apocarboxypeptidase A anc carboxypeptidase A which was inactivated by treatment with the affinity label, N-bromoacetyl-N-methyl-L-phenylalanine, are demonstrated by gel filtration experiments. Morever, competitive binding studies reveal that the latter derivative, in which the binding pocket is presumably blocked by reagent, binds inhibitor nearly as strongly as does the native enzyme, and differences in free energy of association being only 0.4 kcal/mol of a total binding energy of - 11 kcal/mol. A model is proposed to account for both the tight binding of inhibitor to the N-bromoacetyl-N-methyl-L-phenylalanine derivative and the involvement of the active site of arsanilazocarboxypeptidase A. It is suggested that the inhibitor fits into a shallow depression at the active site of the enzyme but does not penetrate into the binding pocket.
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PMID:Carboxypeptidase inhibitor from potatoes. Interaction with derivatives of carboxypeptidase A. 93 26

The study dealt with the level of and diurnal alterations in the concentration of tryptophan, free tryptophan and tyrosine in the blood plasma of 20 inhibited depression patients and 10 healthy controls. The results suggested that there was no distinct relationship between either the total plasma tryptophan or plasma tyrosine level and depression. On the other hand, the free plasma tryptophan level was, at all the times of day at which measurements were made, either significantly or almost significantly higher in the patients than in the controls. It was further found that the results of measurement were related to the patients' clinical improvement, as measured by the Hamilton test, in such a way that after four weeks of treatment the free plasma tryptophan level in 'poorly improved' patients continued to be significantly higher in comparison with the controls, whereas the values for the 'well improved' patient group did not differ greatly from the corresponding values for the control group any longer. It may be hypothesized that the rise in the free plasma tryptophan in depressive patients might represent an effort made by the peripheral body to compensate for the slowed-up serotonin metabolism of the brain, whereby the tryptophan mobilized from the periphery would serve as a sort of 'endogenous antidepressant' provided by the organism itself.
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PMID:The daily rhythm of plasma tryptophan and tyrosine in depression. 94 98

Lisuride hydrogen maleate induced stereotyped behaviour in normal as well as in reserpinized mice. It antagonized the motor depression and hypothermia induced by reserpine. On i.p. administration the compound was about as effective as apomorphine and D-amphetamine. As with apomorphine and in contrast to D-amphetamine the effects of lisuride hydrogen maleate in reserpinized mice were not impaired by additional treatment with alpha-methyl-p-tyrosine methylester. In untreated mice, the substance was very potent in lowering body temperature with significant hypothermia measured after dosages as low as 0.10 mg/kg i.p. Occurrence of stereotyped behaviour and hypothermia could be prevented by the dopaminergic antagonist haloperidol. From these data it is concluded that lisuride hydrogen maleate in addition to its interaction with serotoninergic systems is a potent dopaminergic agonist with a probably direct action on dopaminergic receptors. Further arguments in support of such an action of lisuride hydrogen maleate are, in addition to biochemical data, its serum prolactin lowering effect in rats, its strong emetic action in dogs and its effects on rat behaviour.
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PMID:Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivative, in mice. 94 66

The effect of a compound stimulating central dopaminergic structures, 1,3-dimethyl-5-adamantanamine (D-145), on the intensity of fluorescence in catecholaminergic nerve endings in some regions of the rat brain, mainly in the striatum and hypothalamus, was investigated with the modificated histofluorescence technique of Falck and Hillarp. D-145 (20 mg/kg), 2-3 hr after the administration depressed the intensity of catecholamine (CA) fluorescence in caudate-putamen (CP) and hypothalamic paraventricular nucleus (PVH). A blockade of dopamine (DA) receptors with spiperone (SPIRO, 2 mg/kg, 5 min before D-145) abolished the D-145 effect in PVH, thus indicating an indirect effect of D-145 on PVH, via a dopaminergic system. D-145 potentiated the depression of CA fluorescence produced by alpha-methyl-tyrosine methyl ester (H 44/68), 250 mg/kg ip. High doses of the CA synthesis inhibitor (2 X 400 mg/kg ip) prevented the developing of stimulation produced by D-145. These data indicate that the action of D-145 on DA receptors is indirect, via endogenous DA.
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PMID:The influence of 1,3-dimethyl-5-adamantanamine (D-145) on catecholaminergic neurons of the rat brain, Histofluorescence studies. 95 8


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