Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some preparations of both native aspartate transcarbamylase from Escherichia coli and catalytic subunit have fewer tight binding sites per oligomer for carbamyl-P than the number of catalytic peptide chains. In contrast, the number of sites for the tight-binding inhibitor N-(phosphonacetyl)-L-aspartate does equal the number of catalytic chains in each case. Binding of the labile carbamyl-P was determined using rapid gel filtration, with conversion to stable carbamyl-L-aspartate during collection. Native enzyme (six catalytic chains) obtained from cells grown under the conditions of J.C. Gerhart and H. Holoubek (J. Biol. Chem. (1967) 242, 2886-2892) has 5.4 tight sites for carbamyl-P at pH 8.0 (KD = 9.9 muM), whereas native enzyme from cells grown with higher concentrations of glucose, uracil, and histidine (to yield more enzyme per unit volume of culture) has only 1.9 tight sites at pH 8.0 (KD = 4.6 muM) and only 2.3 tight sites at pH 7.0 (KD = 2.6 muM). At pH 8.0, catalytic subunit (three catalytic chains) obtained from the former native enzyme has 2.2 tight sites for carbamyl-P (KD = 2.4 muM) and the number of sites is 2.3 in the presence of 35 mM succinate, whereas catalytic subunit obtained from the latter native enzyme has 1.8 tight sites (KD = 3.6 muM) in the absence of succinate and 2.3 tight sites in its presence. The number of tight binding sites is also less than the number of subunit peptide chains in 19F nuclear magnetic resonance experiments performed with catalytic subunit and two fluorinated analogs of carbamyl-P at comparable concentrations of analogs and active sites. A model is proposed in which incomplete removal of formylmethionine from the NH2 termini of the enzyme under conditions of extreme depression affects affinity for ligands.
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PMID:Aspartate transcarbamylase of Escherichia coli. Heterogeneity of binding sites for carbamyl phosphate and fluorinated analogs of carbamyl phosphate. 0 9

Fourteen di- and tripeptide analogues of MIF, Pro-Leu-Gly-NH2, have been synthesized and assayed for inhibition of oxotremorine-induced tremor. Replacement of Pro by HCO-Pro or cyclopentanecarboxylic acid gave inactive analogues, while some peptides of the general structure less than Glu-Leu-Gly-NR1R2 were highly active. Thus, R1 = C3H8 and R2 = H gave 4 times the activity of MIF, R1 = I-C3H8 and R2 = H gave 13 times the activity of MIF, and R1 = R2 = CH3 gave 29 times the activity of MIF. cyclo(-Pro-Leu-), Pro-Lys-Gly-NH2, and Pro-Arg-Gly-NH2 had no activity. Apparently, small modifications in the structure of MIF can yield highly active analogues with potential clinical value, e.g., in the treatment of Parkinson's disease or mental depression.
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PMID:Tripeptide analogues of melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) as inhibitors of oxotremorine-induced tremor. 4 28

In two experiments with milk cows with permanent rumen fistula it was investigated whether, apart from urea being unpalatable, further physiologic parameters are responsible for the reduced feed intake. In experiment I the cows received 2, 3 resp 4% urea orally with barley coarse meal, or an equivalent amount was given continuously from the beginning of the feeding over a period of three hours through the fistula. When 2, 3 resp. 4% urea were given orally, the consumption went down in the first 30 min to 58, 52 resp. 40%. When urea was given rumenally, no depression of the consumption could be observed. There were distinct relations with the NH3-concentration in the rumen fluid. At 20 to 35 mg per 100 ml there was no resp. a slight depressioon only and at 40 mg a significant depression. When the concentration rose to greater than 50 mg, consumption was stopped. In experiment II the rumenal application of urea began two hours before the feeding. The high NH3-level shortly after the beginning of feeding (58 mg/100 ml) caused a stop in the feed consumption. No relation could be observed between the urea concentration in veinous blood and the feed intake.
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PMID:[Effective factors for the reduced feed intake of milk cows fed with rations containing urea]. 50 90

1. The use of Li pre-treatment in rats before high pressure oxygen exposure has been reported effective in controlling convulsions. This is an effect which is better demonstrated if exposure to oxygen follows shortly after Li injection than exposure following several hours later. 2. This study has investigated the hypothesis that the protective action of Li may be exerted, in the short term, by its removing ammonia from the blood and alleviating the latter's known toxic action. 3. A normal Li distribution time profile in unstressed rat brain and blood following intraperitoneal injection has been established. Brain and blood ammonia, amino acids and Li concentrations were also measured in Li-treated animals exposed and convulsed by oxygen. These measurements were made both shortly (15 min) and also several hours after (24 hr) Li treatment. Ammonia and amino acid values in Li-protected groups were compared to normal unstressed animal values and also to values in animals convulsed by oxygen unprotected by Li pre-treatment. 4. In rat brain abd blood significant (P less than 0-001) elevation of ammonia and glutamine and depression of gamma-amino butyric acid (brain only) and glutamate was noted following oxygen treatment in unprotected animals. Prior injection of Li 15 min before high pressure oxygen exposure delayed convulsions twice as long. Additionally if these animals were only exposed to oxygen for a period of time equal to that which would normally produce convulsions in unprotected animals, brain and blood ammonia and amino acids were maintained near to unstressed animal levels. Concomitantly, blood Li concentrations were considerably depressed below the values one would expect from the previously determined Li distribution time profile. 5. In rats exposed to high pressure oxygen 24 hr after Li treatment there was no protective action against high pressure oxygen convulsion, rather a potentiating effect for convulsion was seen. 6. These data present compelling evidence for the controlling effect of Li in rats, on rising blood ammonia concentration which occurs in high pressure oxygen exposure. The effect might well be due to the known chelating properties of Li with ammonia.
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PMID:Lithium protection against oxygen toxicity in rats: ammonia and amino acid metabolism. 97 69

Substitution of ammonium ions for sodium ion initially potentiated and then depressed twitch tension of the frog sartorius muscle. The extent of potentiation and the rate of depression of the twitch were dependent upon the concentration of ammonium ions. Ammonium ion depolarized individual muscle fibers in proportion to concentration. Maximum depolarization (33 mV) occurred in muscles equilibrated in 120 mM ammonium-Ringer for 30 min. At the higher concentration of ammonium (72--120 mM), the potentiation was quickly reversed and the tension response was eliminated completely. The gradual loss of twitch tension was accompanied by progressive decrease in the electrical excitability of individual muscle fibers. Raising the extracellular calcium concentration fivefold reduced the twitch-depressant effect of ammonium ions by maintaining excitability of the muscle fibers. Caffeine contractures (3 and 10 mM) in muscles preequilibrated in 72 mM ammonium-Ringer developed similar tensions to paired controls muscles, but the onset of tension was more rapid in the ammonium-treated muscle. It was concluded that the depression of tension could be accounted for by the loss of membrane excitability and that the evidence did not support the hypothesis that ammonium ions acted at other sites in the excitation contraction coupling.
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PMID:Influence of ammonium ions on mechanical and electrophysiological responses of skeletal muscle. 108 37

In the unicellular green alga Chlamydomonas reinhardi (strain y-1), synthesis of the enzymes required for urea hydrolysis is under substrate induction control by urea and under end product repression control by ammonia. Hydrolysis of urea if effected by the sequential action of the discrete enzymes urea carboxylase and allophanate lyase, collectively called urea amidolyase. The carboxylase converts urea to allophanate in a reaction requiring biotin, adenosine 5'-triphosphate, and Mg2+. The lyase hydrolzyes allophanate to ammonium ions and bicarbonate. Neither activity is present in more than trace amounts when cultures are grown with ammonia or urea plus ammonia, or when they are starved for nitrogen for 8 h. Urea in the absence of ammonia induces both activities 10 to 100 times the basal levels. Addition of ammonia to an induced culture causes complete cessation of carboxylase accumulation and an 80% depression of lyase accumulation. Ammonia does not reduce urea uptake by repressed cells, so it does not prevent induction by the mechanism of inducer exclusion. The unicellular green alga Chlorella pyrenoidosa (strain 3 Emerson) also has discrete carboxylase and lyase enzymes, but only the carboxylase exhibits metabolic control.
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PMID:Metabolic control of urea catabolism in Chlamydomonas reinhardi and Chlorella pyrenoidosa. 111 94

Nineteen patients, each hospitalized with a major depressive episode, were deprived of sleep for one night. Ten patients responded with clear improvement in depressive symptoms; the substantial clinical change was transient, usually lasting one day. Those who responded had significantly higher initial depression ratings (P less than .01) and tended to be older than nonresponders who experienced mild increases in irritability, fatigue, and discomfort following sleep deprivation. Amine metabolites, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were not substantially affected by sleep deprivation, although there was a significant interaction of clinical response and direction of 3-methoxy-4-hydroxyphenylglycol (MHPG) change. Sleep deprivation thus produces acute, but only transient improvement in a selected group of severely depressed patients; it appears to be an important tool in the study of the affective disorders.
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PMID:Effects of sleep deprivation on mood and central amine metabolism in depressed patients. 126 78

In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S-form of which is hydroxylated by a P450IIC isozyme, was carried out before amitriptyline therapy. Metabolites were determined in 24-hour urine samples collected on treatment day 8, and the contributions of individual compounds, including the four isomers of 10-hydroxyamitriptyline and 10-hydroxynortriptyline to total excretion were calculated. Formation of (-)-E-10-hydroxyamitriptyline and (-)-E-10-hydroxynortriptyline apparently depends on the activity of cytochrome P450IID6 because negative correlations existed between the log metabolic ratio of dextromethorphan and the relative quantities of these enantiomers. In contrast, correlations were positive for nortriptyline, (+)-E-10-hydroxynortriptyline, (-)-Z-10-hydroxynortriptyline, and (+)-Z-10-hydroxynortriptyline. The mephenytoin hydroxylase seems to participate in side-chain demethylation to the secondary and primary amines, because the log metabolic ratio of mephenytoin correlated negatively with the relative quantity of E-10-hydroxydidesmethylamitriptyline and positively with that of amitriptyline and its N-glucuronide.
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PMID:Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. 142 8

The proximal tubule model of this laboratory [Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F860-F873, 1986] has been updated to examine proposed pathways for Cl- transport. Two additional buffer pairs have been added, i.e., HCO2-/H2CO2 and NH3/NH4+. At the luminal cell membrane Cl-/HCO2- and Cl-/HCO3- exchange are considered as pathways for Cl- entry, whereas at the peritubular membrane, Cl- exit occurs by either Na(+)-2HCO3-/Cl- exchange or K(+)-Cl- cotransport. Calculations with this model indicate that absolute proximal reabsorption of both Na+ and Cl- are critically dependent on the rate of luminal Na+/H+ exchange. In contrast, increases in the coefficient for Cl-/HCO2- exchange have little impact on overall Cl- flux, but, by enhancing base secretion, limit the depression of end-proximal HCO3-. Model calculations confirm those of Preisig and Alpern (J. Clin. Invest. 83: 1859-1867, 1989) showing that their measured value of luminal membrane H2CO2 permeability is inadequate to sustain the transcellular Cl- flux as Cl-/HCO2- exchange. Conversely, with sufficiently high H2CO2 permeability, luminal Cl- uptake is enhanced along the tubule, as HCO2- secretion and luminal acidification increase luminal H2CO2 to values severalfold greater than in glomerular filtrate. At the basolateral membrane, the thermodynamic driving force across the Na(+)-2HCO3-/Cl- exchanger is small. Although its contribution to steady-state Cl- exit may be less than the K(+)-Cl- cotransporter, the Na(+)-2HCO3-/Cl- exchanger can be a mechanism by which cytosolic acidification enhances peritubular Cl- transport, when luminal acidification enhances luminal Cl- uptake. A simulation is presented in which impermeant replacement of luminal Na+ leads to enhanced convective Cl- flux across the tight junction and alkalinization of the lateral interspace. In this setting, cytosolic Cl- depletion via the Na(+)-2HCO3-/Cl- exchanger may mimic luminal membrane Na(+)-Cl- cotransport.
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PMID:Chloride transport in a mathematical model of the rat proximal tubule. 144 69

Only a few of the eight tricyclic antidepressants available today have been studied systematically in the elderly. Tertiary amine tricyclics such as amitriptyline and imipramine have been reported to be effective in depressed geriatric patients, but because of their potential for side effects, it is not advisable to use them in the elderly. Desipramine has a less toxic side effect profile, especially with respect to anticholinergic effects, but its efficacy has not been well studied. This does not mean, however, that it is not an effective drug for the elderly depressed. Nortriptyline is the tricyclic that has been the most studied. The results of those studies show that it should be recommended as an antidepressant for older patients. It is effective in both the acute and continuation treatment of depression in the elderly. As far as its use in maintenance treatment, the results are mixed but at this moment there is nothing with which to compare it. It has a favorable side effect profile: low anticholinergic activity; relatively few cardiac side effects, even in patients with preexisting cardiac disease; and relatively less orthostatic hypotension. Nortriptyline also has the virtue of an established therapeutic range for its steady-state plasma level. The role of its 10-hydroxy metabolite needs to be further explored, but when its contribution to efficacy and toxicity is better understood, it may be possible to use nortriptyline in a more precise and safe way in elderly patients. The bulk of evidence suggests, partly by default, that nortriptyline should probably the tricyclic-of-first-choice in treating an elderly patient with major depression.
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PMID:Using tricyclic antidepressants in the elderly. 160 Apr 82


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