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)

1. The shift in d.c. potential in dorsal roots (EC50 8.0 microM +/- 0.9 s.e. mean, n = 5) or depression of the C elevation of the compound action potential (EC50 3.0 microM +/- 0.3, n = 7) have been used to measure the depolarizing action of kainate on dorsal root C fibres of immature (3 to 5 day old) rats. Depolarization of motoneurones was measured from the shift in d.c. potential in ventral roots. 2. 6-Cyano-7-nitroquinoxaline,2-3,dione (CNQX) (pA2 5.78 +/- 0.06, n = 8) and 6-nitro-7-suplhamobenzo(f)quinoxaline-2,3-dione (NBQX) (pA2 5.75 +/- 0.04, n = 7) had similar potencies as antagonists of kainate at dorsal root fibres. The potency of NBQX as a kainate antagonist was similar also at motoneurones (pA2 5.72 +/- 0.07, n = 3). At motoneurones, NBQX was less potent as an antagonist of domoate (pA2 5.29 +/- 0.05) and more potent as an antagonist of S-alpha-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (pA2 6.80 +/- 0.09) than as an antagonist of kainate. 3. Application of L-glutamate, quisqualate and RS-AMPA to dorsal roots produced only short lasting depolarizations but kainate concentration-effect plots were shifted to the right in the presence of these three agonists (pA2 5.08 +/- 0.08, (n = 3), 5.59 +/- 0.04, (n = 4) and 4.46 +/- 0.04 (n = 4) respectively). Slopes of dose-ratio against concentration were significantly less than one for the latter antagonism. 4. The amplitude of depolarizations induced by L-glutamate, AMPA and quisqualate were increased up to ten fold and those induced by kainate up to two fold following treatment of dorsal roots with concanavalin A. The duration of the responses was increased also by the latter treatment. Folowing 85 s applications of glutamate, quisqualate, AMPA and kainate the mean respective times (s +/- s.e.mean (n))taken for responses to decay to half the peak amplitude were increased from 63 +/- 7 (10), 86 +/- 17 (4),95 +/- 19 (4) and 135 +/- 3 (12) to 202 +/- 49 (10), 147 +/- 7 (4), 160 +/- 13 (6) and 163 +/- 10 (10). Under similar conditions the mean decay time of y-aminobutyric acid-induced responses was 145 +/- 7 (10). This was not significantly altered by concanavalin A treatment.5. Application to dorsal roots of L-aspartate at concentrations up to 5 mm (with or without concanavalin A treatment), the selective metabotropic agonist 1S,3R-trans-1-aminocyclopentane-1,3-dicarboxylate (1 mM,) and D-serine (20 pM) in the presence or absence of N-methyl-D-aspartate (NMDA,500 pM) neither depolarized the preparations nor shifted the kainate concentration-effect plot.6. It is concluded that primary afferent C fibres possess only one type of non-NMDA receptor which is activated strongly by domoate or kainate but only weakly by AMPA. This receptor is readily desensitized by glutamate, quisqualate or AMPA and it is less readily desensitized by kainate.
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PMID:A comparison of the actions of agonists and antagonists at non-NMDA receptors of C fibres and motoneurones of the immature rat spinal cord in vitro. 809 24

1. We have investigated the role of changes of potassium efflux in the inhibition of uterine force produced by cyanide. K+ efflux (86Rb) was measured from pregnant and non-pregnant rat myometrial strips during metabolic inhibition with cyanide and following manoeuvres to displace intracellular pH (pHi). 2. Cyanide greatly reduced or abolished spontaneous contractions. If the membrane was depolarized directly at this stage (by elevating external K+) then contraction redeveloped. This suggests that the initial depression of force is due to a failure of membrane excitation. 3. Cyanide reversibly increased 86Rb efflux (30-35%) in both pregnant and nonpregnant uteri and contraction was reduced. The increase in 86Rb efflux with cyanide was not secondary to changes of membrane potential as it also occurred in both high-K+ and Ca(2+)-free solutions. 4. Glibenclamide (20 microM), an antagonist of K+ATP channels, reduced the cyanide-evoked increase of 86Rb efflux by about 50%. The glibenclamide-insensitive component of efflux persisted in a Ca(2+)-free solution. Despite its action on 86Rb efflux, glibenclamide did not restore contraction. 5. Intracellular pH falls during metabolic inhibition. We therefore investigated whether reducing pHi (in the absence of cyanide) had an effect on 86Rb efflux. Application of the weak acid butyrate (60 mM, at constant external pH, 7.4) had no significant effect on 86Rb efflux. Thus it is unlikely that the acidification in hypoxia contributes to the increased K+ efflux. 6. Intracellular alkalinization produced by the weak base trimethylamine (60 mM) increased the frequency of uterine contraction and the 86Rb efflux. However, there was no effect on the 86Rb efflux in a Ca(2+)-free solution. The increased efflux is therefore presumably a consequence of the increased frequency. 7. It is concluded that metabolic inhibition produced by cyanide, produces an increase in K+ efflux from the myometrium. Part of this efflux is glibenclamide sensitive. This increased K+ efflux will lead to hyperpolarization of the myometrial membrane and thus decrease excitation. Thus reduced surface membrane excitability will contribute to the fall of force in hypoxia; specifically it may cause the initial loss of spontaneous contractions in the uterus.
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PMID:Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus. 822 44

The effect of metabolic inhibition on macroscopic and single-channel K+ currents in isolated rabbit portal vein myocytes was investigated by patch-clamp technique. Depression of adenosine triphosphate synthesis was produced by 2-deoxy-D-glucose (10 mM) and either cyanide (2 mM) or dinitrophenol (50 microM). Outward quasi-steady-state current evoked by a ramp protocol and outward time-dependent current during step depolarizations were increased during metabolic inhibition. The reversal potential for quasi-steady-state current shifted negatively toward equilibrium potential of K+ during treatment consistent with a role for K+ conductance and hyperpolarization of membrane potential. The macroscopic K+ current affected was 1) voltage dependent, 2) inhibited by intracellular Ca2+ chelation and low tetraethylammonium ion (1 mM) but unaffected by 4-aminopyridine (2 mM), and 3) associated with a rise in intracellular Ca2+ assessed by indo 1. Metabolic inhibition caused an increase in voltage-dependent large-conductance K+ channel (120-130 pS) activity in cell-attached patches of myocytes bathed in physiological solution (140 mM K+ in pipette). The channels were blocked in a flickery fashion by tetraethylammonium ion (0.5 mM) and inhibited with charybdotoxin (100 nM). We conclude that metabolic inhibition increases the activity of large-conductance Ca(2+)-activated K+ channels in vascular smooth muscle.
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PMID:Metabolic inhibition enhances Ca(2+)-activated K+ current in smooth muscle cells of rabbit portal vein. 828 58

To examine the effect of hypoxia confined to the ventrolateral medulla we microinjected NaCN into the cat medulla (1.0 mm below the ventral surface) unilaterally and investigated cardio-respiratory changes. We studied anesthetized artificially ventilated animals and measured the electrical activity of phrenic and cervical sympathetic nerves and blood pressure. Histotoxic hypoxia depressed phrenic amplitude and elevated sympathetic tone and blood pressure. These responses were obtained predominantly from the region 5.0-8.0 mm caudal to the foramen caecum and 3.0-5.0 mm lateral to the midline (intermediate area). A study with 14C-cyanide showed that total and covalently bound cyanide was confined within a 1 mm diffusion sphere following microinjection. Isolated areas in both rostral and caudal medulla responded to cyanide with elevated sympathetic tone in the absence of phrenic nerve depression, suggesting dissociation of respiratory and vasomotor responses to hypoxia. Thus, the respiratory depression and vasomotor excitation produced by central hypoxia can be reproduced by hypoxia limited to discrete regions of the ventrolateral medulla.
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PMID:Intramedullary sodium cyanide injection on respiratory and vasomotor responses in cats. 836 18

The pharmacological actions of cyanide on respiratory activity have been known for some time and are attributed mainly to effects on peripheral chemoreceptors. In the studies reported here, we have examined the acute central effects of cyanide when applied topically to the ventral surface of the medulla (VMS) and when administered into the spinal intrathecal space at the C5-T3 level on activities of the phrenic nerve, diaphragm, parasternal intercostal, triangularis sterni, and transversus abdominis muscles. Topical application of 10-100 micrograms (10 microliters of 1-10 mg/ml) cyanide to the intermediate area of the VMS decreased respiratory activity by > 50%, and expiratory muscles were more sensitive to inhibition than inspiratory muscles. The onset of depression of phrenic nerve or respiratory muscle activity occurred within 20 s of administration, and the effects reversed after washout. In contrast, intrathecal administration of cyanide in doses of 10-100 micrograms (100 microliters of 0.1-1 mg/ml) increased electrical activity of the respiratory muscles. Diaphragm activity changed from 17 +/- 2 to 42 +/- 8 (SE) units (P < 0.01), parasternal intercostal activity increased from 18 +/- 3 to 46 +/- 9 units (P < 0.01), and expiratory activity of the chest wall and abdominal muscles increased from 9 +/- 2 to 39 +/- 10 units (P < 0.05). Both topical application on the VMS and intrathecal administration of cyanide caused an increase in arterial blood pressure and a slight insignificant acceleration of heart rate. These data suggest that cyanide acting on the VMS causes respiratory depression and enhancement of sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Central and spinal effects of sodium cyanide on respiratory activity. 845 72

Mitochondrial protein synthesis is acutely depressed during anoxia-induced quiescence in embryos of Artemia franciscana. Oxygen deprivation is accompanied in vivo by a dramatic drop in extramitochondrial pH, and both of these alterations strongly inhibit protein synthesis in isolated mitochondria. Here we show that the oxygen dependence is not explained simply by blockage of the electron transport chain or by the increased redox state. Whereas oxygen deprivation substantially depressed protein synthesis within 5 min and resulted in a 77% reduction after 1 h, aerobic incubations with saturating concentrations of cyanide or antimycin A had little effect during the first 20 min and only a modest effect after 1 h (36 and 20% reductions, respectively). Yet the mitochondrial NAD(P)H pools were fully reduced after 2-3 min with all three treatments. This cyanide- and antimycin-insensitive but hypoxia-sensitive pattern of protein synthesis depression suggests the presence of a molecular oxygen sensor within the mitochondrion. Second, we show for the first time that acidification of extramitochondrial pH exerts inhibition on protein synthesis specifically through changes in matrix pH. Matrix pH was 8.2 during protein synthesis assays performed at the extramitochondrial pH optimum of 7.5. When this proton gradient was abolished with nigericin, the extramitochondrial pH optimum for protein synthesis displayed an alkaline shift of approximately 0.7 pH unit. These data suggest the presence of proton-sensitive translational components within the mitochondrion.
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PMID:Acute depression of mitochondrial protein synthesis during anoxia: contributions of oxygen sensing, matrix acidification, and redox state. 863 50

The effect of supermethrin on the overall health with respect to weight gains, diet intake, triad values (body temperature, pulse rate and breathing rate) and potential intoxication signs was investigated in sheep of the Slovak Mertino breed (age of 8 months, males and females) during 6-week feeding of the insecticide supermethrin (Research Institute of Chemical Technology, Bratislava). This insecticide supermethrin contains a cyanide group in its molecule and can be included in the group of type II pyrethroids. It is an analog of cypermethrin and it has a different proportion of cis- and trans-isomers. Supermethrin mixed with molasses feed M was administered daily at a dose of 50 mg/kg (about 1/70 of LD50) to five sheep of experimental group I, at a dose of 200 mg/kg (about 1/15 of LD50) to five sheep of experimental group II, and the dose increased from 200 mg to 300 mg/kg l.w. (about 1/20 of LD50) since the fourth week of trial. The main signs of its toxic action involved depressive effects on weight gains (Fig. 4) Over the whole period of trial, the live weight rose by 5.44 +/- 1.94 kg in control group, by 2.66 +/- 1.48 kg in experimental group I, which equates a significant decrease by 51.10% and only 0.34 +/- 0.95 kg in experimental group II, which equates a decrease in weight gains by up to 93.75% against the control. We do not believe that the growth depression can be related to diet intake. There were no larger differences in feed intake between the experimental groups and the control. The growth depression was caused by incessant diarrhea. The patho-morphological examination did not reveal hyperemia and/or intestinal inflammation, the histological examination did not show any lesions of epithelium in the intestinal mucosa. An increase in supermethrin dose from 200 to 300 mg/kg l.w. resulted in signs coming from the CNS. Hypersensibility manifested by moderate unrest, head and neck shaking after auditory, and especially after touch stimuli was observed. This tremor was increasing to became spontaneous 3-4 days before trial termination. The above findings clearly suggest that supermethrin administration at lower doses has harmful effects primarily on the digestive tract, but at higher doses these effects are more intensive accompanied by the effects on the CNS. No negative effects on pulse rate (Fig. 1), breathing rate (Fig. 2) and internal body temperature (Fig. 3) were recorded.
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PMID:[The effect of supermethrin, an insecticide, on health status indicators in sheep during subchronic poisoning]. 865 91

1. Diets containing supplements of selenium (10 mg/kg as sodium selenite), copper (500 mg/kg as copper (II) sulphate) and sodium nitroprusside (SNP 300 mg/kg) as a source of cyanide, were fed singly and in all possible combinations to chicks from 14 to 35 d of age. 2. Both copper and SNP individually alleviated the growth depression caused by excess selenium but interacted adversely with one another. The effect of SNP was to decrease liver selenium but copper increased it. Despite this contrast it is suggested that both achieve their beneficial effects through influences on the fraction of liver selenium that can be reduced to volatile forms by hydrochloric acid and zinc. 3. In a second experiment the effects of diets containing additional selenium (2 mg/kg as sodium selenite or selenomethionine) with or without additional copper (100 mg/kg) or SNP (100 mg/kg) on selenium incorporation into eggs were compared. 4. SNP reduced incorporation from selenite whereas copper had no effect. However, copper reduced the incorporation from selenomethionine into protein fractions of egg white as much as SNP.
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PMID:Interactions between dietary selenium, copper and sodium nitroprusside, a source of cyanide in growing chicks and laying hens. 883 30

The mechanism by which adenosine accumulates in the hippocampal slice during energy deprivation was investigated by examining the adenosine A1 receptor mediated depression of synaptically evoked field potentials in the CA1 area. Blocking of the mitochondrial electron transport chain with 200 microM sodium cyanide or mitochondrial uncoupling with 50 microM 2,4-dinitrophenol both produced a rapid depression of synaptic transmission that was antagonised by 1 microM 8-cyclopentyl-1, 3-dimethylxanthine, an adenosine A1 receptor antagonist. Cellular ATPase inhibition or elevation of cytosolic phosphocreatine failed to alter the 2,4-dinitrophenol induced depression of synaptic transmission. Attempts to block mitochondrial ATP synthesis with 3 microM oligomycin or 75 microM atractyloside did not cause depression of synaptic transmission. 100 microM iodotubercidin, an adenosine kinase inhibitor, alone produced a depression of synaptic transmission that was completely reversed by 1 microM 8-cyclopentyl-1,3-dimethylxanthine; however, a simultaneous or independent episode of hypoxia surmounted the adenosine A1 receptor antagonism and produced approximately 50% depression of synaptic transmission. Depression of synaptic transmission by hypoxia, cyanide or 2,4-dinitrophenol is a result of rapid adenosine accumulation and activation of extracellular adenosine A1 receptors. Although this early depression of synaptic transmission is a consequence of inhibition of normal mitochondrial function, it is not a result of depletion of cytosolic ATP, since attempts to preserve ATP did not maintain synaptic transmission during mitochondrial poisoning, and inhibitors of oxidative phosphorylation did not produce synaptic depression.
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PMID:Mechanism of adenosine accumulation in the hippocampal slice during energy deprivation. 901 69

The rapid suppression of CNS function produced by cyanide (CN) was studied by field, intracellular, and whole-cell recording in hippocampal slices (at 33-34 degrees C). Population spikes and field EPSPs were depressed by 4-5 min bath applications of 50-100 microM CN (IC50 was 18 miroM for spikes and 72 microM for EPSPs). The actions of CN were reversibly suppressed by the adenosine antagonists 8-sulfophenyltheophylline (8-SPT; 10 microM) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.2 microM), potentiated by the adenosine transport inhibitor dipyridamole (0.5 microM), but unaffected by the KATP channel blocker glyburide (10 microM). Therefore the CN-induced reductions of synaptic efficacy and postsynaptic excitability-demonstrated by synaptic input:output plots-are mediated mainly by adenosine. In whole-cell or intracellular recordings, CN depressed EPSCs and elicited an increase in input conductance and an outward current, the reversal potential of which was approximately -90 mV (indicating that K+ was the major carrier). These effects also were attenuated by 8-SPT. In the presence of 1 mM Ba, CN had no significant postsynaptic action; Cs (2 mM) also prevented CN-induced outward currents but only partly blocked the increase in conductance. Another 8-SPT-sensitive action of CN was to depress hyperpolarization-activated slow inward relaxations (Q current). At room temperature (22-24 degrees C), although it did not change holding current and slow inward relaxations, CN raised the input conductance; this effect also was prevented by 8-SPT (10 microM), but not by glyburide (10 microM). Adenosine release thus appears to be the major link between acute CN poisoning and early depression of CNS synaptic function.
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PMID:Adenosine release mediates cyanide-induced suppression of CA1 neuronal activity. 906 96


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