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 understanding of the effects of cannabinoids in human subjects has been obscured by a lack of knowledge about how the various active principles from marijuana act at the cellular level in the brain. For this reason the present study was undertaken to determine the effects of cannabinoids on the enzymes associated with the synaptic membranes. Electron micrographic analysis was performed to determine the purity of synaptic membrane preparations from rat brain, and subsequently such preparations were subjected to additions of ethanol, Tween-80, 80% glycerol, and either delta-tetrahydrocannabinol, 11-hydroxy-delta-tetrahydrocannabinol, or cannabinol. Both sodium and potassium activated ATPase (Na, K-ATPase), and Mg-ATPase were measured as the micrometer orthophosphate (P) released per minute per microgram membrane protein and these specific activities of the enzymes expressed as absolute values and as the percentage depression brought about by the cannabinoids. The ATPase spcific activities are taken from the rate curve over a 30-min incubation time. Additionally, synaptic membrane acetylcholineesterase specific activity was measured by continuous rate enzyme assay. While as low as 10 M delta-tetrahydrocannabinol showed appreciable decrements in both the membrane-bound ATPases, the other cannabinoids did not show such a great depression in enzyme activity. The specific activity of acetylcholinesterase, which is weakly bound to the membrane, showed only slight or no changes in activity with the various cannabinoids. It was additionally shown that the cannabinoids, delta-tetrahydrocannabinol in particular, bound to the synaptic membranes almost irreversibly in the in vitro system, and that the vehicle for dissolving the cannabinoids, while used as background control values when calculating the percentage decrements in enzyme specific activity, did vary the effects on the ATPase enzymes in particular. These data are discussed in relation to psychotomimetic activity of the cannabinoids.
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PMID:Effects of cannabinoids on synaptic membrane enzymes. I. In vitro studies on synaptic membranes isolated from rat brain. 14 40

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

Bone marrow fragments from 10 patients with a megaloblastic anaemia due to vitamin B12 or folate deficiency were studied by electron microscopy and electron microscope autoradiography. A proportion of the erythroblasts showed ultrastructural abnormalities. Some of the cells containing autophagic vacuoles, large siderosomes, iron-laden mitochondria, irregularly shaped nuclei, membrane-bound nuclear clefts, or incomplete nuclear membranes were found to be capable of DNA, RNA and protein synthesis. Other cells showed advanced degenerative changes such as the distension of the perinuclear space, the clumping of cytoplasmic organelles near the nucleus and a reduction in the electron density and ribosome content of the cytoplasm. Most of these grossly abnormal cells suffered from either a marked depression or an arrest in protein and RNA synthesis, and were presumably destined for phagocytosis by reticulum cells.
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PMID:Electron microscope and high resolution autoradiographic studies of megaloblastic erythropoiesis. 40 60

1. The effects of external medium calcium concentration, the ionophore A(23187) and lanthanum on the rate of renin release in vitro were studied with particular emphasis on results obtained from isolated superfused glomeruli of rat kidneys.2. The response to reduction in superfusate calcium concentration from 2 mM was a graded and reversible increase in the rate of renin release. An increase in release was detectable at 0.2 mM calcium; a threefold increase was found 36 min after a change from 2 mM calcium to calcium-free superfusate. A similar relative increase in release resulted from reductions from 0.1 mM to zero calcium, but the absolute amounts of renin released were greater in this latter series. Renin release from kidney cortical slices similarly increased in response to calcium-free incubation medium.3. The effects of A(23187) on renin release were modest. Changing from 2 mM calcium during control periods to calcium-free Ringer with A(23187) added caused an attenuated and more delayed increase in release than the change to calcium-free Ringer without ionophore. This difference in response was abolished when glomeruli were superfused with 0.1 mM calcium during the preceding 1 hr control period. There was no significant difference in renin release from glomeruli exposed to calcium-free EGTA-Ringer with and without A(23187) in the 2 mM calcium series; in the 0.1 mM calcium series the increase in release following a shift to calcium-free EGTA-containing superfusate with A(23187) added was significantly greater than in the absence of the ionophore.4. Addition of lanthanum (1 or 0.05 mM) to calcium-containing as well as calcium-free superfusate resulted in a significant depression of renin release. Subsequent removal of the lanthanum did not restore the rate of release unless EGTA was added; in the latter case a massive increase in renin release occurred resulting in a marked depletion of the remaining renin content of the glomeruli.5. It is concluded that calcium influences renin release by a direct action on the juxtaglomerular cells. The data support the previous suggestion that basal renin release is a function of active, calcium-dependent cell volume regulation - swelling causing an increase in the release; and further suggest that membrane-bound calcium has a direct effect on the cell membrane permeability to renin.6. The results exclude that calcium-stimulated exocytosis is responsible for basal renin release from the juxtaglomerular cells adhering to isolated glomeruli.
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PMID:Studies on the mechanism of renin release from isolated superfused rat glomeruli: effects of calcium, calcium ionophore and lanthanum. 41 32

The effects on spontaneous and ionophore-induced transmitter release of the inorganic dye, ruthenium red (RuR), a known inhibitor of calcium binding sites, were observed at the frog sartorius neuromuscular junction using intracellular recording techniques. Both crude and purified RuR, at concentrations of 1 and 5 micron depressed or blocked spontaneous release of acetylcholine (ACh) and reduced postsynaptic sensitivity to ACh, the crude dye being more potent than the pure. Pretreatment of muscles with RuR prevented the catastrophic reaction of junctions to 100 micron X537A ionophore. Increased levels of Ca2+ restored spontaneous transmitter release to control levels after depression or blockade by RuR. It was concluded that RuR blocks a critical membrane-bound binding site for calcium which is necessary for quantal release of transmitter.
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PMID:Depression of spontaneous and ionophore-induced transmitter release by ruthenium red at the neuromuscular junction. 48 23

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

Zein accumulation patterns during mutant and normal maize endosperm development were determined. Accompanying an increase in the number of floury-2 alleles present in the endosperm was a well-defined stepwise depression in zein accumulation. Analysis of the zein accumulated in endosperms containing zero, one, two, and three doses of the floury-2 allele by sodium dodecylsulfate--polyacrylamide gel electrophoresis revealed a proportionate reduction in the two major zein components, Z1 and Z2. In contrast, the relative proportions of the minor zein bands were altered. Membrane-bound polysomes isolated from kernels of floury-2 and normal maize were predominantly large size classes. The presence of increasing numbers of the floury-2 allele in the endosperm decreased recovery of membrane-bound polysomal material in a stepwise fashion. However, major alterations in polysome size-class distributions were not observed. The reduction in membrane-bound polysome material correlated linearly with reductions in in vitro zein synthesis and in vivo zein accumulation.
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PMID:Effects of floury-2 locus on zein accumulation and RNA metabolism during maize endosperm development. 64 84

Polyene antibiotics (levorin, nistatin, amphotericin B) inhibit protein synthesis at concentrations decreasing 14C-amino acid incorporation into Candida albicans protoplasts by 30--60%, the depression of membrane permeability beginning earlier than protein synthesis inhibition. Fractionation of protoplast lysates revealed that protein synthesis by free ribosomes was inhibited by antibiotics stronger than in case of membrane-bound ribosomes. It is supposed that different response of two ribosome classes for polyenes-induced damages is due to different sensitivity of free and membrane-bound ribosomes to the decrease of intracellular K+ concentration.
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PMID:[Effect of polyene antibiotics on protein synthesis by free and membrane-bound ribosomes of Candida albicans]. 79 40

The effects of a short-term in vivo administration of two liver tumour promoters (phenobarbital and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane on rat liver endoplasmic reticulum Ca(2+)-ATPase were investigated. The specific activity values of this membrane-bound enzyme significantly decreased (P less than 0.01) by 51% for phenobarbital-treated rats and by 48% for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane-treated rats compared with control animals. The depression of liver endoplasmic reticulum Ca(2+)-ATPase appears to be a manifestation of the toxicological effect of tumour promoters.
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PMID:Depression of the Ca(2+)-ATPase activity of the rat liver endoplasmic reticulum by the liver tumour promoters, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane and phenobarbital. 134 71

Denervated fast-twitch rabbit muscles were progressively losing their fresh weight and the yield of sarcotubular protein was increasing. The activity of Ca(2+)-ATPase was affected but very slightly, the basal Mg(2+)-ATPase and the Mg(2+)-ATPase/Ca(2+)-ATPase ratio however increased together with a simultaneous depression of the membrane-bound acetylcholinesterase activity. We did not observe any differences in density properties of sarcotubular fractions between control and denervated muscle. However, a relative enrichment in SM and H fraction could be seen after denervation with small changes in the content of the Ca(2+)-pump protein, increased levels of calsequestrin and cholesterol, mostly in the heavy and the SM fraction. After denervation the binding sites for 3H-PN-200-110 did not show any changes in receptor affinity, but the number of putative Ca(2+)-channels increased twice along with a depression of 3H-ouabain binding sites. We suggest that the denervation of fast-twitch muscle leads to the hypertrophy of the junctional sarcoplasmic reticulum and the T-system. Changes in the cholesterol content, in the number of putative Ca(2+)-channels and in Na+, K(+)-ATPase can affect the muscle contraction.
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PMID:Effects of denervation on the contents of cholesterol and membrane systems involved in muscle contraction in rabbit fast-twitch sarcotubular system. 165 Jul 29


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