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)

We have devised an improved high pressure liquid chromatographic technique whereby serotonin, nucleosides, cyclic nucleotides, namely cAMP and cGMP, and 5'mono-, 5'di-, and 5'tri-nucleotides can be analyzed. The cyclic nucleotides have been measured in picomolar quantities. All nucleotides can be quantitated in a single step separation in 75 min using a 0.0015 M phosphoric acids vs. 1M pH 4.8 ammonium phosphate gradient. 5/10 ml of platelet-rich plasma furnishes an adequate sample for complete analysis. Nucleotide levels in platelets from 16 normal donors expressed in 10(11) platelets are as follows: cAMP, 6.32 (4.15) nanomoles and AMP, 0.32 (0.14); ADP, 2.48 (0.67); ATP 3.78 (0.68); GDP 0.38 (0.07) and GTP, 0.45 (0.07) micromoles. ADP and ATP values are lower than those previously published. However, the total nucleotide level approaches published values. Upon aggregation with thrombin, approximately 50% of ADP and 40% ATP is releaseed. Release is complete by 2 min. Thrombin is the most potent releasing agent with collagen and ADP occupying an intermediate role and epinephrine being the least effective. Upon aggregation cyclic AMP levels diminish along the other nucleotides. Patients with asthma showed depression of ADP, ATP, GDP and GTP levels.
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PMID:Measurement of nucleotide pools in platelets using high pressure liquid chromatography. 57

Pyruvate and K-ferricyanide stimulation of net ATP and 2,3-bisphosphoglycerate synthesis is very probably due to enhancement of glyceraldehyde 3-phosphate dehydrogenase activity. Significant peculiarities in the K-ferricyanide effect and its depression by non-penetrating-SH inhibitors at low concentrations were noted and suggested that membrane-bound enzymes play a substantial part in the synthesis of ATP and 2,3-bisphosphoglycerate. Experiments with isolated ghosts showed their ATP-and 2,3-bis-phosphogylcerate-building capacity. Pulse-labeling with 32P-Pi and determination of specific radioactive in intracellular inorganic phosphate and ATP-gamma-P demonstrated that the ferricyanide-stimulated compartment utilizes only intracellular inorganic phosphate for ATP (and 2,3-bisphosphoglycerate) synthesis, and does so only when extracellular inorganic phosphate is present.
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PMID:The role of red cell membrane in the regulation of glycolysis and the 2,3-bisphosphoglycerate-cycle. 59 59

The paper reports an analysis of the relationship between deltamuH the proton electrochemical potential difference, and deltaGp, the phosphate potential. Depression of deltamuH and deltaGp has been obtained by titration with: (a) carbonylcyanide trifluoromethoxyphenylhydrazone; (b) nigericin (+ valinomycin); (c) KCl (+ valinomycin); and (d) rotenone. The uncoupler depresses deltamuH more than nigericin (+ valinomycin), KCl (+ valinomycin) and rotenone at equivalent deltaGp. The deltaGp/deltamuH ratio is about 3 at high values of deltamuH. When deltaGp and deltamuH are depressed by nigericin (4 valinomycin) the deltaGp/deltamuH ratio remains constant. When deltaGp and deltamuH are depressed by uncouplers, the deltaGp/deltamuH ratio increases hyperbolically tending to infinity while deltamuH tends to zero. The absence of constant proportionality between deltaGp and deltamuH indicates that the proton gradients driving ATP synthesis presumably operate within microscopic environments.
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PMID:Proton electrochemical gradient and phosphate potential in mitochondria. 62 18

1. The influx of a number of amino acids into squid giant axons has been studied. Particular emphasis has been placed on glycine and to a lesser extent glutamate. 2. To facilitate the study of the uptake of 14C-labelled amino acids a technique was devised in which the 14C taken up was measured directly in the intact axon with a glass scintillator fibre. This technique gave results similar to the usual technique in which the axoplasm was extruded for the assay of radioactivity. 3. The changes in glycine influx with extracellular glycine concentration suggests that two saturating components are present, one with high affinity and one with low affinity. 4. The glycine influx does not seem normally to be sensitive to the removal of extracellular sodium by replacement with choline. A Na-sensitive component appeared, however, after a period of immersion in artificial sea water. There was also some depression of glycine influx if Na were replaced by Li. 5. Glutamate uptake was greatly reduced by removal of extracellular Na in confirmation of work by Baker & Potashner (1973). Orthophosphate uptake was also greatly reduced by removal of extracellular Na. 6. CN reversibly inhibited glycine uptake after a delay, indicating that part of the uptake mechanism may require ATP. 7. 14C-labelled glycine injected into squid axons was found not to exchange to any serious extent with other compounds over periods of a few hours. The glycine efflux could therefore be studied. This was found to be markedly increased by extracellular glycine and by certain other neutral amino acids applied extracellularly in the artificial sea water. 8. The enhanced glycine efflux in extracellular glycine was not affected by ouabain and CN. 9. It is suggested that glycine uptake in squid axons involves two components. One is sensitive to CN and ouabain and probably derives energy from ATP break-down. The other is probably an ATP independent exchange diffusion system in which other amino acids as well as glycine can exchange for glycine. Both these systems are independent of extracellular Na concentration. A third Na-dependent system may appear under certain conditions.
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PMID:Glycine fluxes in squid giant axons. 67 Dec 72

Rats fed a special liquid fat diet had a higher level of liver triglycerides than rats fed a normal solid chow diet. The ingestion of ethanol induces a concomitant increase in hepatic triglycerides and a depression of ATP levels. Pure adenine base administered orally produces a significant reduction of hepatic triglycerdies and partially restores ATP levels in the chronic ethanol treated rat. Comparable doses of oral ATP are not effective. Pure guanine base and GTP failed to inhibit the ethanol-induced fatty liver and ATP depression.
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PMID:The effect of purine bases and nucleotides on ethanol-induced fatty liver syndrome. 67 63

Drug effects on myocardial contractile function are obviously of considerable practical importance for the toxicologist. The basic mechanism of such actions must reside at some point in the metabolism of cardiac muscle. Interference in the liberation of energy from the fuels that the heart uses may be implicated. It is possible that drugs may interfere with the storage (conservation) of that energy as the high energy phosphates (ATP and CP). Finally, the utilization of that stored energy by the contractile proteins themselves may be altered. The latter process is highly dependent on intracellular calcium ion kinetics. Anesthetic drugs, which produce reversible depression of myocardial contractile function is a dose-dependent fashion, have been shown to interfere to some extent with all three processes. However, the most important mechanism probably involves utilization of energy and intracellular calcium ion movement. A basic knowledge of the biochemistry of cardiac muscle is necessary for the understanding of drug action and toxicity at the subcellular level.
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PMID:Myocardial metabolism for the toxicologist. 72 Mar 13

Treatment of 24 male patients with 3 g/day of xanthinol nicotinate did not change the in vitro measurements of ADP-induced platelet aggregation but produced a marked inhibition of collagen-induced platelet aggregation. This effect may be connected with the drug-induced depression of the ATP level in platelet-rich plasma. Changes in the platelets in the patients' blood or in the lipid composition and the concentration of uric acid in their serum were ruled out as reasons for the decrease of the collagen-induced aggregation. The activity of the three serum enzymes y-GT, GOT, and GPT and the concentration of the blood sugar did not change.
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PMID:Effect of xanthinol nicotinate treatment on platelet aggregation. 84 33

L5178Y mouse lymphoma cells normally appear to possess two functional thymidine kinase alleles (TK+/+). TK-deficient (TK-/-) clonal lines can be derived from these cells by treatment with EMS or other mutagens. Mezger-Freed [12] has argued that such stable phenotypic variants do not arise as the result of gene mutations but instead represent epigenetic events such as normally occur during differentiation without any permanent gene alteration. If this be so, then rare TK+/- revertants arising in TK-/- cultures should possess TK enzyme identical with one of those present in the original TK+/+ cells, since only depression of the TK gene is involved. Our studies show that this is not the case. Among the mutant TK enzymes analyzed in vitro (those from parental TK+/- lines, each derived in turn from separate TK-/- lines) differences were found in (1) solubility in saline; (2) solubility in 3 M LiCl; (3) Km's; and (4) ATP-Mg2+ requirements. These findings were incompatible with a non-mutational model for the production of these stable variants and, in conjunction with reversion-rate data, they tended to favor either direct structural gene modifications or mutations affecting the expression of adult and fetal enzymes.
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PMID:Evidence for chemically-induced structural gene mutations at the thymidine kinase locus in cultured L5178Y mouse lymphoma cells. 89 58

By Ussing's flux chamber method the effect of ATP and acetylcholine (ACh) on the sodium transport was studied in bullfrog colon. The results obtained are as follows; 1. ATP added to the mucosal medium caused biphasic changes in the transmural potential difference (P.D.) and short-circuit current (S.C.C.), although serosal ATP was ineffective. After an initial rapid and transient rise, both the P.D. and S.C.C. increased in parallel to reach a peak in about 10 min suggesting that the tissue conductance is little affected by ATP. Addition of ouabain to the serosal fluid depressed both the P.D. and S.C.C. and abolished the electrical responses to ATP. The application of ouabain to the mucosal side did not cause any significant depression. These results can be explained in terms of stimulation of sodium pump by ATP added to the mucosal medium. 2. ACh added to either the mucosal or the serosal medium caused increased in the P.D. and the S.C.C. The serosal application was more effective than the mucosal application. The increase in S.C.C. was more remarkable than that in the P.D., indicating an increase in the tissue conductance. It is suggested that ACh stimulates ion transport systems by changing the membrane permeability of the colon.
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PMID:[The effect of ATP and acetylcholine on the sodium transport in bullfrog large intestine (author's transl)]. 108 21

Adult rhesus monkeys were subjected to complete cerebral ischemia for one hour and subsequent recirculation for up to 24 h. Animals with signs of functional recovery (e.g. spontaneous EEG activity) exhibited a partial replenishment of cellular energy sources (ATP, phosphocreatine) and a progressive normalization of cerebral lactate levels. Glucose and pyruvate concentrations showed a transient increase over control values during the early stages of postischemic recirculation. Monkeys without functional recovery lacked a significant resynthesis of energy-rich compounds; adenine nucleotides continued to decrease and lactate concentrations were higher than in animals subjected to ischemia without recirculation. Cerebral polysome profiles remained unaltered during the ischemic period but in all animals a marked disaggregation of polyribosomes with a concomitant increase in ribosomal subunits occurred after the onset of recirculation. In monkeys with indications of functional recovery these changes were reversible but a normal polysome profile was only observed after 24 h of recirculation. The results obtained indicate a postischemic depression of protein synthesis due to an inhibition of peptide chain initiation. After recirculation of the brain for 3-6 h there was evidence for an induction of enzymes involved in polyamine synthesis (ornithine decarboxylase and S-adenosylmethionine decarboxylase). No changes in the activity of these enzymes were observed at the end of the ischemic period, indicating that during complete cerebral ischemia not only the synthesis but also the catabolism of proteins is inhibited.
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PMID:Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. 115 69


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