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)

The effect of gentamicin on both glutamate synthesis and glutamate deamination was studied in kidney-cortex mitochondria and tubules isolated from both control and gentamicin-treated animals. In kidney-cortex mitochondria which were permeabilized in order to make a free access of substrates and antibiotic to the glutamate dehydrogenase, gentamicin appeared to be a very potent inhibitor of glutamate synthesis, resulting in about 60% decrease of the enzyme activity at 5 mM concentration. Other aminoglycoside antibiotics decreased the enzymatic activity, in the following order: gentamicin > neomycin = tobramycin = kanamycin > biodacyna > amikacin > streptomycin. This, in principle, corresponds to their known nephrotoxic potential observed in vivo. The inhibitory action of antibiotics was abolished by neither ADP nor leucine, allosteric activators of glutamate dehydrogenase. Surprisingly, gentamicin did not decrease the rate of ammonia formation from glutamate when added to both renal tubules and mitochondria isolated from control rabbits. This indicates that the antibiotic exerts its inhibitory effect on glutamate dehydrogenase activity in the direction of glutamate synthesis only. In contrast, the rate of both glutamate deamination and glutamate synthesis was about 40% lower in renal tubules and mitochondria isolated from kidney-cortex of animals which were given antibiotics for 10 days. In view of these results it seems that (i) the depression of ammoniagenesis in gentamicin-treated animals may be due to a decrease of glutamate dehydrogenase content and (ii) under conditions in vitro the aminoglycoside inhibits the enzyme activity in the direction of glutamate synthesis while it does not affect the glutamate deamination.
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PMID:Differential in vivo and in vitro effect of gentamicin on glutamate synthesis and glutamate deamination in rabbit kidney-cortex tubules and mitochondria. 136 90

To determine the effects of dietary protein level on cardiac and hepatic mitochondrial oxidative phosphorylation, chicks were fed on semi-purified diets of different protein levels (7, 25, 43 and 61% of metabolizable energy content) for 7, 14 and 21 d. All diets were formulated to contain equivalent fat, mineral and vitamin contents on a gross energy basis. Cardiac and hepatic mitochondrial oxidative phosphorylation rates were assessed polarographically with pyruvate and malate as substrates. Cardiac mitochondria isolated from chicks fed on a 43 or 61% protein-energy diet for 7 d exhibited significantly reduced ADP:oxygen (ADP:O) ratios when compared with mitochondria isolated from chicks fed on a lower-protein-energy diet. Feeding low- (7%) protein-energy diets for 14 d resulted in a relatively increased ADP:O ratio in the heart. Responses of ADP:O ratios to protein level in hepatic mitochondria showed more dependency on protein level than in heart muscle; at all feeding periods the ADP:O ratio decreased with an increase in protein level. As a result, ATP synthesized in the liver, expressed as nmol/mg mitochondrial protein per min, significantly decreased with increased dietary protein level. A parallel correlation was observed, in chicks fed on diets with different levels of protein, between ADP:O ratio for liver mitochondria and body fat. These results suggest that the reduction in oxidative phosphorylation in the heart and liver of animals fed on a higher protein-energy diet may partly contribute to the depression of body fat.
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PMID:Dietary protein level alters oxidative phosphorylation in heart and liver mitochondria of chicks. 139 Jun 19

1. Orthophosphate (P(i), 0.1-2.0 mM) was photogenerated within the filament lattice of isometrically contracting glycerinated fibres of rabbit psoas muscle at 10 and 20 degrees C. The P(i) was produced by laser flash photolysis of the photolabile compound 1-(2-nitrophenyl)ethylphosphate (caged P(i)). Caged P(i) caused a depression of tension that was much smaller than that caused by P(i). 2. Photolysis of caged P(i) produced a decline in isometric force composed of four phases: phase I, a lag phase (e.g. 1-4 ms at 10 degrees C) during which force did not change; phase II, an exponential decline by as much as 20% of the pre-pulse force; phase III, a partial force recovery (0-3% of the pre-pulse force); and phase IV, a further slow (0.5-3 s) decline to the steady value. Phases I, III and IV were largely independent of [P(i)] and are likely to be indirect effects caused by the caged P(i) photolysis. 3. Both the rate and amplitude of phase II depended markedly on [P(i)]. The amplitude of phase II was similar to the reduction of steady-state force by P(i). The rate of phase II increased with increasing temperature and [P(i)]. At high [P(i)] the rate began to saturate, and approached limits of 123 s-1 at 10 degrees C and 194 s-1 at 20 degrees C. 4. The rate of phase II was independent of sarcomere overlap, while the amplitude was proportional to tension at partial filament overlap. A control experiment using caged ATP showed that phase II was not produced by the photolytic by-products or the light pulse. The results suggest that phase II is associated with the force-generating transition of the cross-bridge cycle. 5. Sinusoidal length oscillations at 0.5 and 2 kHz were used to measure muscle stiffness during phase II. Stiffness declined in a single exponential phase, with the same time course as phase II of the tension transient. The change in stiffness was 83 +/- 6% (mean +/- S.E.M., n = 10, 0.5 kHz) of the change in tension when both signals were normalized to their pre-flash values. 6. Analysis of the data shows that two steps are involved in force generation and P(i) release. The non-force exerting AM-ADP-P(i) cross-bridge state first isomerizes to form a force-exerting cross-bridge state (AM'-ADP-P(i)). P(i) is then released to form a second force-generating state, AM'-ADP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reversal of the cross-bridge force-generating transition by photogeneration of phosphate in rabbit psoas muscle fibres. 140 12

1. Pyruvate kinase was partially purified from the foot, mantle, and digestive gland of active and aestivating snails. 2. At pH 7.0 the apparent Km values for phosphoenolpyruvate (PEP) were 0.064 mmol/l for the enzyme from foot and 0.071 mmol/l for the enzyme from mantle; those for ADP were 0.35 mmol/l for the foot enzyme and 0.33 mmol/l for the mantle enzyme. 3. Both enzymes were inhibited by alanine, and this could be reversed by fructose 1,6-bisphosphate (FBP), although FBP alone was a weak activator. 4. Decreasing the pH to 6.5 markedly increased the inhibition by alanine and reduced the response to FBP. 5. The enzymes from these tissues of aestivating snails showed a small decrease in their affinity for PEP and a small increase in the effectiveness of alanine as an inhibitor. 6. These changes are indicative of a down-regulation of this enzyme which is consistent with the observations in other species during metabolic depression. 7. In contrast the enzyme from the digestive gland of active animals showed sigmoidal saturation kinetics for PEP with a S0.5 of 1.2 mmol/l, but had a markedly higher affinity for PEP, S0.5 = 0.20 mmol/l during aestivation. This may be indicative of other metabolic changes occurring in the digestive gland.
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PMID:The effects of aestivation on the catalytic and regulatory properties of pyruvate kinase from Helix aspersa. 152 37

Methapyrilene (MP) is a rat-specific liver carcinogen that alters mitochondrial number and morphology both in vivo and in vitro. This biological phenomenon may be due to the effects of MP on mitochondrial function. To test this hypothesis, studies were conducted to examine the effects of MP on DNA and protein synthesis and respiration in isolated mitochondria. DNA and protein synthesis activities were measured using [3H]thymidine and [3H]leucine incorporation. Mouse liver mitochondria were also examined for comparison since no tumor formation or alterations in mitochondrial morphology have been associated with MP treatment in mice. A significant decrease in basal DNA and protein synthesis levels was observed in mitochondria isolated from rats and mice following in vivo MP treatment. This effect could not be reproduced when mitochondria were exposed to 0 or 100 microM MP following isolation, despite the presence of an S9 activation system. Electron microscopic examinations were performed on isolated rat mitochondria and revealed morphologic differences between mitochondria from naive and MP-treated rats. Although significant differences in State 3 and State 4 respiratory rates were noted, the respiratory control ratio, ADP/O ratio, and uncoupler-stimulated respiratory rates were unaffected. Results demonstrate that: (1) MP irreversibly depresses DNA and protein synthesis in a majority of mitochondria, despite only localized morphologic changes; (2) these changes are not reflected by a decrease in respiratory function; and (3) depression of DNA and protein synthesis does not correlate with carcinogenic susceptibility.
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PMID:Effects of methapyrilene measured in mitochondria isolated from naive and methapyrilene-treated rat and mouse hepatocytes. 152 42

The tone of vascular smooth muscle is influenced by factors released from the endothelium, including endothelin (ET)-1 and endothelium-derived relaxing factor (EDRF). To better understand the interactions between these two mediators, we examined the release of both immunoreactive ET-1 (ir-ET-1) and EDRF from bovine aortic intact endothelium. Bovine aortas were opened longitudinally, washed, and clamped with the endothelium uppermost between two plates. The upper plate contained six openings forming identical and independent wells of endothelial cell monolayer. In experiments examining the release of EDRF, measured as accumulated NO2- and NO3- (NO chi -), we found that ET-3, calcium ionophore A23187 (A23187), acetylcholine (ACh), or ADP caused significant increase in NO chi- release, whereas ET-1 did not. These were significantly reduced in the presence of the EDRF/NO synthase inhibitor, NG-methyl-L-arginine (L-NMA). In a parallel series of experiments measuring EDRF release by stimulation of guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in rat fetal lung (RFL)-6 cells, ET-3 but not ET-1 was also found to be active as a releaser of EDRF. A23187 caused an increase of ir-ET-1 release, whereas ACh, ADP, or the NO-containing compound sodium nitroprusside decreased the release of ir-ET-1. The depression in ir-ET-1 release in the presence of ACh or ADP was not seen when the endothelium was treated with L-NMA. When the cells were pretreated with 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP), the release of ir-ET-1 in response to A23187 was significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions of endothelins and EDRF in bovine native endothelial cells: selective effects of endothelin-3. 159 Apr 65

The aim of this study was to determine the significance of the "coronary factor" in patients with essential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organization criteria). Silent, ie, painless ST-segment depression, was found in 34 patients on whom echocardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included 201Tl stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catecholamines and beta-endorphins were obtained in blood samples during silent ischemia. 201Tl scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 mumol/L adenosine diphosphate; one patient in this group had coronary atherosclerosis. LVH and the platelet aggregation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and beta-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different pathogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia.
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PMID:Silent myocardial ischemia in patients with essential hypertension. 163 37

Infection of beagles with an opossum-derived strain of Trypanosoma cruzi (Tc-O) results in features of early and chronic chagasic cardiomyopathy, that is, increases in PR interval, atrioventricular block, and frequent ventricular premature contractions, ventricular tachycardia, and decreased left ventricular ejection fraction. These signs are not observed in animals infected with a canine strain of T. cruzi (Tc-D). To understand the biochemical basis for these early cardiac effects, we examined the beta-adrenergic adenylate cyclase complex in myocardial membranes prepared from animals infected with either of the two strains. In animals infected with Tc-O (symptomatic), the maximum velocity (Vmax) decreased and concentration of agonist resulting in 50% of Vmax (Kact) increased for isoproterenol-dependent adenylate cyclase activity; in animals infected with Tc-D (asymptomatic), Vmax and Kact for isoproterenol were unchanged from control, uninfected animals. beta-Receptor density decreased by 20% in symptomatic animals with no change in affinity, whereas no differences were observed between uninfected and infected asymptomatic animals. A complex pattern of changes was apparent in the guanine nucleotide binding protein, Gs, in the setting of infection. Alterations in cholera toxin-dependent ADP-ribosylation patterns as well as immunochemical detection with anti-G alpha s antisera suggested a change in the biochemical nature of the Gs species and not necessarily a physical loss of this protein. Reconstitution of adenylate cyclase activity in cyc- membranes demonstrated a decrease in hormone-sensitive Gs activity in membranes prepared from symptomatic animals without a change in activity demonstrable in the presence of Gpp(NH)p. Collectively, the results suggest that the depression in beta-adrenergic adenylate cyclase activity associated with symptomatic infection of beagles with T. cruzi occurs primarily as a result of changes in the Gs protein complex, most likely resulting in an uncoupling of the beta-adrenergic receptor from the Gs protein.
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PMID:Myocardial beta-adrenergic adenylate cyclase complex in a canine model of chagasic cardiomyopathy. 164 78

CK-2289 is an inhibitor of type III cyclic 3'5'-adenosine monophosphate phosphodiesterase with potential utility in the treatment of congestive heart failure. We compared CK-2289 to milrinone and enoximone in several pharmacological models. Intravenous administration of CK-2289 to pentobarbital-anesthetized dogs (0.03 to 1 mg/kg) produced dose-related increases in myocardial dP/dTmax and decreased mean arterial blood pressure, similar to milrinone and enoximone. However, CK-2289 was 3-9 times more potent than either agent as a positive inotrope. Intraperitoneal and oral administration of CK-2289 and milrinone to mice produced central nervous system depression. Administered intravenously. CK-2289 and milrinone (1 mg/kg) inhibited, whereas enoximone (1 mg/kg) enhanced, guinea-pig gastric acid secretion. CK-2289 (0.01 to 0.3 mg/kg) and milrinone (0.03 to 1 mg/kg), given intravenously, did not affect neurotransmission to the rabbit sciatic nerve-gastrocnemius muscle preparation. Neither CK-2289 nor milrinone (100 microM) inhibited sympathetic neurotransmission, alpha 1-, muscarinic and thromboxane receptors. Both compounds relaxed canine arteries and veins. CK-2289 was devoid of effects on non-vascular smooth muscles of guinea-pig vas deferens and uteri and rabbit bronchi. CK-2289 (1 to 100 microM), milrinone and enoximone inhibited human platelet aggregation produced by adenosine diphosphate and sodium arachidonate. These data suggest that CK-2289 should be devoid of adverse renal, neural, smooth or skeletal muscle or gastrointestinal side effects associated with milrinone and enoximone therapy.
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PMID:Pharmacological comparison of CK-2289, an inodilator agent, with milrinone and enoximone. 165 60

The effect of normothermic ischemia and ischemia/reperfusion on the function of cardiac sarcoplasmic reticulum (CSR) was investigated using a modified Langendorff perfusion of isolated rat hearts. The function of the CSR was assessed by the oxalate-supported Ca2+ uptake rate of ventricular homogenates. The contribution of the ryanodine-sensitive portion of the CSR was determined by using 20 microM ruthenium red or 625 microM ryanodine to close the CSR Ca2+ release channel. The Ca2+ uptake rate of the CSR decreased progressively with increasing duration of ischemia, but this depression was much less when uptake was assayed in the presence of ryanodine. The depression in CSR Ca2+ uptake preceded ischemic contracture. Ryanodine and ruthenium red stimulated uptake almost equally in control hearts, but ruthenium red was much less effective than ryanodine after ischemia. This difference could not be overcome by increasing the ruthenium red concentration. These results confirm the suggestion that the Ca2+ release channel is inappropriately opened after ischemia. The CSR uptake rates were almost completely restored at 15 minutes of reperfusion after 5 and 10 minutes of ischemia but were only partially restored after 15 minutes of ischemia. At reperfusion, mechanical function (end-diastolic pressure and peak systolic developed pressure) was markedly depressed after only 15 minutes of ischemia. The degree of "stunning" correlated well with the depression of CSR function in individual hearts. The decreased Ca2+ uptake of the CSR was not due to a buildup of ADP in the homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversibility of the effects of normothermic global ischemia on the ryanodine-sensitive and ryanodine-insensitive calcium uptake of cardiac sarcoplasmic reticulum. 172 84


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