UMLS:C0011570 - FACTA Search

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

Evoked release of transmitter at the squid giant synapse was examined under conditions where the calcium ion concentration in the presynaptic terminal was manipulated by inhibitors of calcium sequestration. Simultaneous intracellular recordings of presynaptic and post-synaptic resting and action potentials were made during bath application of one of the following metabolic inhibitors: sodium cyanide (NaCN), carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP); ruthenium red (RuR) and sodium-free (lithium) sea water. Cyanide and lithium sea water reversibly depressed the post-synaptic potential (p.s.p.) whilst RuR and FCCP blocked the evoked post-synaptic response irreversibly. The progressive reduction of p.s.p. amplitude was accompanied by a reversible increase in synaptic delay. The time course of block of the p.s.p. was similar for different agents and dependent on the rate of presynaptic activity (30-40 min at 0.01 Hz). Recovery of the post-synaptic action potential following block by cyanide and lithium sea water was obtained within 40 min and 5 min respectively. Synaptic depression by the metabolic inhibitors does not result from changes in presynaptic resting or action potentials, nor from a change in post-synaptic receptor sensitivity. The post-synaptic response to the local ionophoresis of L-glutamate was unchanged following inhibition of evoked release of transmitter by cyanide. Injections of EGTA into presynaptic terminals poisoned by cyanide produced transient increases in p.s.p. amplitude, suggesting that cyanide is having its effect through raising intracellular calcium rather than lowering ATP. Control experiments injecting EGTA into unpoisoned nerve terminals showed no apparent effect on evoked transmitter release.
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PMID:Inhibitors of calcium buffering depress evoked transmitter release at the squid giant synapse. 241 46

The effects of sodium selenite on the neuromuscular junction of the phrenic nerve-diaphragm of the mouse were studied. Nerve-evoked twitches of the diaphragm of the mouse, the frequency of miniature endplate potentials, the quantal content of endplate potentials and the compound action potentials of the axon were measured. Sodium selenite induced a slight increase of the amplitude of the twitch, followed by twitch depression. The amplitude of the twitch, increased by selenite, became more prominent after the suppression of the twitch induced by cadmium ions, d-tubocurarine or magnesium ions. It appeared that the increased amplitude of twitch was due to the facilitation of transmitter release, since selenite significantly increased the frequency of miniature endplate potentials, and the amplitude and quantal content of endplate potentials; the amplitude and half decay time of miniature endplate potentials were unaffected. Twitch depression induced by selenite was enhanced by ammonium ions, high potassium and low magnesium and attenuated by high calcium. During the period of gradual depression of the twitch, selenite decreased the amplitude of compound action potentials of the phrenic nerve axon and caused the disappearance of endplate potentials. Ammonium ions enhanced the blockade of axonal conduction induced by selenite. Moreover, the depolarizing agents, ammonium and high potassium also induced an initial increase of twitch amplitude followed by depression of the twitch. These findings indicate that selenite probably alters the release of the transmitter by depolarizing the nerve membrane. The effects of selenite were antagonized by glutathione and cyanide, suggesting that the binding of selenite to sulfhydryl groups of the membrane was essential for inducing its pharmacological actions.
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PMID:Effects of sodium selenite on neuromuscular junction of the mouse phrenic nerve-diaphragm preparation. 247 66

Transverse slices from guinea pig hippocampi were exposed to micromolar concentrations of sodium cyanide while neural and synaptic function were monitored in the CA1 region. Cyanide concentrations between 10 and 200 microM rapidly depressed synaptic transmission between Schaffer collateral-commissural fibers and CA1 pyramidal cells. Analysis of input/output curves revealed that the suppression had two components, a decrease in EPSP generation and an increase in action potential threshold. Direct electrical excitability of axons was not affected. At concentrations to 500 microM, cyanide had no effect on antidromic activation of pyramidal cells. At 1000 microM, cyanide caused a moderate depression of the antidromic response in one slice while having no effect in one other. In some experiments, postsynaptic responses in the gyrus dentatus (GD), evoked by perforant path stimulation, were recorded simultaneously with CA1 responses during cyanide application. GD was found to be less sensitive to cyanide than CA1. All cyanide effects reversed rapidly and completely upon washout. These findings suggest that cyanide has a direct effect on neurons not mediated by its inhibition of metabolism.
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PMID:The effects of cyanide on neural and synaptic function in hippocampal slices. 255 76

A total of 108 growing albino rats was used to evaluate the dietary interactions of the major lima bean antinutritional factors trypsin inhibitor (TI), haemagglutinin (Hgg) and cyanide (CN) with respect to their effects on pancreatic and intestinal alpha-amylase activities. The results indicate that when fed at the same level of activity as found in the raw lima bean (RLB) these factors had no significant (p greater than 0.05) influence on pancreatic alpha-amylase activity whether acting individually or in combination. However, when acting alone, CN appeared to depress pancreatic amylase level more than when interacting with TI or Hgg or both. Amylase activity was significantly (p less than 0.01) depressed by the dietary treatments in both the small and large intestine while caecal levels were not. The most severe depression in amylase activity was elicited by the RLB diet. The haemagglutinin-containing diets appeared generally associated with lower levels of intestinal amylase activity. From the present finding it is suggested that these factors alone cannot fully account for the magnitude of the depression of intestinal amylase activity which is contingent upon the ingestion of RLB by experimental rats.
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PMID:Dietary interactions of lima bean (Phaseolus lunatus) trypsin inhibitor, haemagglutinin and cyanide. Part 2. Effect on pancreatic and intestinal alpha-amylase (EC 3.21.1.1) in growing albino rats. 278 18

Metabolic regulation of contractility in vascular smooth muscle was studied in the spontaneously active rat portal vein using respiratory depression by cyanide (0.2-2.0 mM) as a model for tissue hypoxia. Intracellular recordings of electrical activity were done with concomitant registration of force development. Average membrane potential in the absence of cyanide was -61 +/- 1 mV (n = 27). Addition of cyanide to normal Krebs solution resulted in a reduction of force amplitude and the number of action potentials per burst, with a relatively more pronounced effect on the mechanical activity. At moderate levels of inhibition of force amplitude the frequency of spontaneous bursts of action potentials transiently increased concomitant with a slight depolarization, but after prolonged (15-20 min) exposure to cyanide the membrane repolarized to the level prior to cyanide addition and the burst frequency decreased to be equal to or lower than that in the absence of cyanide. Higher concentrations of cyanide totally inhibited spontaneous mechanical and electrical activity. In contrast to the results with glucose, it was found that when beta-hydroxybutyrate was used as substrate the addition of 2 mM cyanide led to a marked hyperpolarization (13 +/- 1 mV) after total inhibition of spontaneous activity. The hyperpolarization was not prevented by administration of 4-aminopyridine (2.5 mM) or tetraethylammonium (4-6 mM) prior to the addition of cyanide. To investigate the effects of increased metabolic demand on the relation between force and membrane potential in cyanide-treated muscle, high-K+ (40 mM) contractures were studied. Contractures were associated with depolarization of 34 +/- 3 mV (n = 5). 1 mM cyanide reduced the amplitude of the contractures to about 9% of control with a moderate reduction in the amount of depolarization (28 +/- 1 mV, n = 5). It is concluded that the decrease of mechanical activity during respiratory inhibition may partly reflect a reduction in the number of spikes per burst but that other mechanisms, independent of membrane activity, also contribute to the inhibition. The increase of glycolysis during respiratory inhibition seems to prevent more pronounced changes in membrane potential.
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PMID:Electrical and mechanical responses to inhibition of cell respiration in vascular smooth muscle of the rat portal vein. 280 Nov 56

The mechanism of uncoupling of oxidative phosphorylation by carbonyl cyanide p-trifluoromethoxy)phenylhydrazone (FCCP), a typical weak acid protonophore, oleic acid, a fatty acid, and chloroform, a general anesthetic, has been investigated by measuring in mitochondria their effect on (i) the transmembrane proton electrochemical potential gradient (delta mu H) and the rates of electron transfer and adenosine 5'-triphosphate (ATP) hydrolysis in static head, (ii) delta mu H and the rates of electron transfer and ATP synthesis in state 3, and (iii) the membrane proton conductance. Both FCCP and oleic acid increase the membrane proton conductance, and accordingly, they cause a depression of delta mu H [generated by either the redox proton pumps or the adenosinetriphosphatase (ATPase) proton pumps]. Although their effects on ATP synthesis/hydrolysis, respiration, and delta mu H are qualitatively consistent with a pure protonophoric uncoupling mechanism and an additional inhibitory action of oleic acid on both the ATPases and the electron-transfer enzymes, a quantitative comparison between the dissipative proton influx and the rate of either electron transfer or ATP hydrolysis (multiplied by either the H+/e- or the H+/ATP stoichiometry, respectively) at the same delta mu H shows that the increase in membrane conductance induced by FCCP and oleic acid accounts for the stimulation of the rate of ATP hydrolysis but not for that of the rate of electron transfer. Chloroform (at concentrations that fully inhibit ATP synthesis) only very slightly increases the proton conductance of the mitochondrial membrane and causes only a little depression of delta mu H.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uncoupling of oxidative phosphorylation. 1. Protonophoric effects account only partially for uncoupling. 282 53

To examine the cellular mechanism of urinary acidification in detail, micropuncture studies were performed on the in situ bullfrog proximal tubule with nigericin-based pH microelectrodes. Pencil-type double-barreled antimony microelectrodes were also used for monitoring pHs of the tubular fluids. Luminal perfusion of 10(-3) M cyanide caused a biphasic change in cell pH (pHi): i.e., early acidification by 0.04 pH unit in 2 min and later alkalinization by 0.04. A profound depolarization of 30-35 mV was observed in the peritubular membrane potential (EM Peri), although the tubular fluid pH (pHTF) was elevated by 0.11 unit. Luminal substitution of 100 mM Na+ by Li+ acidified the cell by 0.06 pH unit with a depolarization of EM Peri by 8 mV and an alkalinization of pHTF by 0.10 unit. It is a fact that cellular acidification and luminal alkalinization are in good agreement with the depression of luminal H+ secretory mechanism. Perfusion of 10(-4) M SITS from the peritubular side caused a rise in pHi by 0.04 without appreciable changes in EM Peri in the short period application. Peritubular perfusion of 10(-4) M ouabain lowered the pHi by 0.07 with a resulting depolarization of EM Peri by 15.4 mV, meanwhile, the pHTF, while initially lowered by 0.07 unit, was elevated 4 min later by 0.12. Inhibitions of the peritubular ion transport mechanism caused some pH changes in the same direction, both in the cell interior and the tubular fluid. Further, from the ouabain experiment, it is inferred that some linkages, mediated by Na+ and H+(or HCO3-), would exist between the peritubular and luminal membranes.
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PMID:Regulatory mechanism of cell pH in the renal proximal tubule of bullfrog nephron. 300 93

In the guinea-pig terminal ileum a maximally effective concentration of prostacyclin (PGI2) (1 mumol/l) induced contractions that were partially resistant to tetrodotoxin (TTX) 0.1 mumol/l, to low temperature (20 degrees C) and to atropine (30 nmol/l). Half maximum contractions evoked by PGI2 (20 nmol/l) were abolished by TTX and by low temperature, which did not modify the response to exogenous acetylcholine (ACh), as well as by atropine. Procaine (5-500 mumol/l) caused a concentration-dependent inhibition of contractions induced by PGI2 (20 nmol/l and 1 mumol/l) and by equieffective concentrations of ACh (20 nmol/l and 0.4 mumol/l, respectively). The order of magnitude for this inhibition was ACh 20 nmol/l = PGI2 20 nmol/l greater than PGI2(1) mumol/l greater than ACh 0.4 mumol/l. In preparations exposed to TTX or to low temperature procaine (50 mumol/l) did not affect the residual response to PGI2 (1 mumol/l). Quercetin (1 and 5 mumol/l) inhibited the effect of PGI2 and, at higher concentrations, it also caused partial depression of the responses to ACh. Quercetin did not alter TTX-resistant and low temperature-resistant contractions induced by PGI2 1 mumol/l. Carbonyl cyanide-trifluoro-methoxyphenyl hydrazone (FCCP) (0.1-1 mumol/l) reduced the effect of PGI2 and of ACh to approximately the same extent and inhibited the residual response to PGI2 1 mumol/l in preparations treated with TTX or expressed to low temperature. The present results show that PGI2, besides acting on cholinergic neurons, also exerts a direct effect on smooth muscle cells and FCCP can be used to block this effect. In contrast procaine and quercetin selectively inhibit the ACh-mediated component of PGI2 action.
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PMID:Target sites for the inhibition of prostacyclin effect in guinea-pig ileum. 332 10

Incubation of 25-hydroxyvitamin D3 with kidney cortex mitochondria from 1,25-dihydroxyvitamin D3-treated guinea pigs resulted in the formation of 23,25-dihydroxyvitamin D3 as the major product. The identity of the product was verified by g.c.-m.s. and quantification was performed by h.p.l.c. The rates of the reaction were in the range 1.0-1.8 pmol/min per mg of mitochondrial protein (at 37 degrees C), which were 5-10 times the rates of formation of 24,25-dihydroxyvitamin D3. In mitochondrial preparations from untreated guinea pigs, the rate of 23-hydroxylation was below detection limit (0.02 pmol/min per mg of mitochondrial protein). Fasting the animals for 24 h induced the 23-hydroxylase almost as efficiently as treatment with 1,25-dihydroxyvitamin D3, with a concomitant depression of the 1 alpha-hydroxylase. The 23-hydroxylase reaction required oxidizable substrate, was decreased by low O2 partial pressures and inhibited by CO or the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone. It was stimulated by the respiratory-chain inhibitors rotenone, antimycin A and KCN. These results indicate that the guinea-pig renal mitochondrial 23-hydroxylase is a cytochrome P-450 and that the reducing equivalents are primarily supplied by NADPH via the energy-dependent transhydrogenase.
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PMID:Assay and properties of 25-hydroxyvitamin D3 23-hydroxylase. Evidence that 23,25-dihydroxyvitamin D3 is a major metabolite in 1,25-dihydroxyvitamin D3-treated or fasted guinea pigs. 335 35

The pathophysiology, clinical features, and management of cyanide toxicity are reviewed and sources of cyanide are listed. Cyanide is a deadly poison that is found in many foods and household and industrial products, including some that are readily available. Cyanide binds with cytochrome oxidase, the enzyme responsible for oxidative phosphorylation, and paralyzes cellular respiration. Because the tissues cannot use oxygen that is delivered, aerobic metabolism ceases. The signs and symptoms of cyanide poisoning reflect the extent of cellular hypoxia. Manifestations may include respiratory abnormalities (progressing from tachypnea and dyspnea to respiratory depression and apnea), hemodynamic instability, metabolic acidosis, and, possibly, local irritant effects after oral ingestion of cyanide. The mainstays of therapy are 100% oxygen and specific antidotes to cyanide. Sequential treatment with amyl nitrite by inhalation, intravenous sodium nitrite 3%, and intravenous sodium thiosulfate 25% is directed toward decreasing the amount of cyanide available for cellular binding. Nitrites convert hemoglobin to methemoglobin, which reacts with cyanide to form cyanomethemoglobin. Sodium thiosulfate serves as a source of sulfur groups, which are needed for conversion of cyanide to thiocyanate, a compound that is relatively less toxic and is excreted renally. Supportive care also is important. Cobalt EDTA, hydroxocobalamin, and aminophenols have also been used but are not considered standard treatments. Cyanide poisoning is a medical emergency that requires prompt recognition and immediate and aggressive treatment.
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PMID:Clinical features and management of cyanide poisoning. 353 Jun 15

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