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)

Female C3H/HeJ or CD-1 mice were infected with a sublethal dose of murine cytomegalovirus (MCMV) and then exposed to nickel chloride (NiCl2) or cadmium chloride (CdCl2) intramuscularly (im) or by inhalation. Effects of these treatments on disease susceptibility, virus-augmented and spontaneous natural killer (NK) cell activity, and virus induction of interferon (IFN) were determined. NiCl2 (20 mg/kg, im) enhanced mortality due to MCMV in both mouse strains, and a reduction in virus-augmented NK cell activity was seen at doses as low as 10 mg NiCl2/kg im. At 6.25 mg CdCl2/kg im there was a significant depression of NK cell activity, but there was no effect on mortality due to infection. Effects on NK activity did not appear to be due to effects on IFN production since neither of the metal treatments caused depression of this response. Neither metal when given by inhalation had any effect on these parameters.
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PMID:Effects of NiCl2 and CdCl2 on susceptibility to murine cytomegalovirus and virus-augmented natural killer cell and interferon responses. 244 Jul 51

1. The effects of some divalent cations on the A-current (IA) in cultured rat dorsal root ganglion cells (DRGs) were studied using whole-cell patch recording. 2. IA was not affected by omission of calcium from the external medium; however it was significantly depressed by manganese (10 mM) applied by pressure ejection. This depressant effect of manganese resulted from a depolarizing shift of the activation curve by 17 mV, associated with only a slight reduction of the maximum conductance. At 10 mM manganese also caused a depolarizing shift of the steady-state inactivation curve by 34 mV. Divalent cations other than manganese also gave positive shifts of the steady-state activation and inactivation curves for IA but were of different potency; the sequence was: Cd2+ greater than Mn2+ = Co2+ greater than Mg2+. 3. A dose-response curve for the depolarizing shift of the activation and inactivation curves of IA, as a function of manganese concentration, could be fitted by a single binding site model with an apparent dissociation constant of approximately 17 mM. The depolarizing shift of the inactivation curve was on average twice as large as that of the activation curve. 4. In contrast to its effect on IA, manganese (10 mM) did not cause any appreciable change in the voltage dependence of the activation curve for the delayed rectifier K+ current. 5. A low concentration of manganese (1 mM) increased the amplitude of IA recorded at pre-pulse potentials ranging from -50 to -70 mV. This augmentation of IA resulted from a positive shift of the inactivation curve by 6 mV without an appreciable shift of the activation curve; as a result a population of A-channels is released from inactivation over pre-pulse potentials from -50 to -70 mV. 6. These results show that divalent cations can evoke a depolarizing shift of both the activation and inactivation gates controlling IA; this causes either depression or augmentation of IA, depending on the species and concentration of the divalent cation, and also on the pre- pulse potential used to de-inactivate IA. This modulatory effect of divalent cations on the gating of IA appears to reflect binding to a specific, saturable site, either the A-channel protein itself, or phospholipids electrically close to the gating apparatus.
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PMID:A modulatory action of divalent cations on transient outward current in cultured rat sensory neurones. 245 91

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

1. Propagated Ca-spikes were recorded from isolated cervical sympathetic nerve trunks of the rat when bathed in a solution containing 5 mM Ca2+, 0.5 or 1 microM tetrodotoxin (to block Na currents) and 1 mM 4-aminopyridine (to reduce K currents). 2. Spikes persisted when external Ca2+ was replaced with Sr2+ or Ba2+, but were blocked by the addition of the following inorganic Ca-channel blockers (in descending order of potency): Cd2+ greater than La3+ greater than Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+. 3. Ca-spike amplitude was reduced by up to 90% by (-)-noradrenaline (IC50 1.5 microM). The following sympathomimetic amines imitated this effect (in descending order of potency): clonidine greater than or equal to (-)-adrenaline greater than or equal to [(-)-noradrenaline] greater than or equal to dopamine greater than (-)-phenylephrine greater than or equal to (+/-)-amidephrine. 4. Ca-spike inhibition by (-)-noradrenaline was antagonized by phentolamine (pA2 6.5). Yohimbine was about 10 times weaker than phentolamine; (+/-)-propranolol (1 microM) and prazosin (10 microM) had no clear effect. 5. (-)-Noradrenaline reduced the amplitude of the compound action potential recorded from the superior cervical sympathetic ganglion following supramaximal preganglionic trunk stimulation when recorded in normal Krebs solution and hyperpolarized the ganglion with respect to the post-ganglionic trunk. Depression of the transmitted ganglionic action potential was antagonized by phentolamine (5 microM) but not by yohimbine (1 microM); in contrast 1 microM yohimbine completely prevented the ganglionic hyperpolarization. (-)-Noradrenaline did not hyperpolarize the preganglionic cervical sympathetic nerve trunk under these recording conditions. 6. It is suggested that inhibition of transmitter release from sympathetic preganglionic fibres produced by noradrenaline results from a depression of the voltage-gated Ca current in the fibres and/or their terminals, and that this action is mediated by an alpha-adrenoceptor which does not fully conform to either alpha 1 or alpha 2 subtypes.
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PMID:Inhibition of Ca-spikes in rat preganglionic cervical sympathetic nerves by sympathomimetic amines. 253 83

1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%).
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PMID:Anoxia on slow inward currents of immature hippocampal neurons. 255 81

1. Excitatory postsynaptic potentials (e.p.s.ps) were recorded from the submandibular parasympathetic ganglia of newborn rats (10-20 days old), by intracellular microelectrode recording and a suction electrode to deliver stimulus trains to the lingual nerve (15 stimuli at 0.1, 0.3, 1, 3, and 10 Hz, 22 degrees C). Only evoked responses without voltage-dependent action potentials were analyzed (observed at membrane potentials negative to -70 mV), and e.p.s.p. amplitudes were determined for the plateau responses during each train (5-15th response). 2. Cadmium, an inorganic calcium channel antagonist, reduced e.p.s.p. amplitudes in a dose-dependent manner (Kd 74 microM, P less than 0.01). Nickel (1-300 microM) did not attenuate the amplitude of evoked responses. 3. Verapamil (0.1-30 microM), a phenylamine, had no significant effects upon e.p.s.p. amplitudes at any frequency examined. Higher concentrations of verapamil (100 microM) blocked neurally evoked responses in a manner consistent with the antagonism of voltage-sensitive sodium currents. 4. Diltiazem, a benzothiazepine, reduced e.p.s.p. amplitudes in a dose-dependent manner, the depression being accentuated at high stimulation frequencies (80% block at 30 microM and 10 Hz). The pure (-)-cis enantiomer of diltiazem (10-30 microM) was without effect. 5. Amlodipine, a 1,4-dihydropyridine, did not antagonize synaptic transmission at any stimulus frequency examined (10-30 microM, 0.1-10 Hz, n = 3). 6. Amiloride, a potassium-sparing diuretic, depressed the amplitudes of evoked responses in a dose-dependent manner (one-site Kd 31 microM, P less than 0.005), although the extent of the block was alleviated with high stimulus frequencies. The effects of 30 microM amiloride were unlikely to be of post-synaptic origin as both the amplitudes of miniature e.p.s.ps, and the iontophoretic potentials induced by exogenous acetylcholine, were not attenuated by treatment with this compound. The amiloride derivative, 3',4'-dichlorobenzamil was ineffective in reducing the amplitude of e.p.s.ps (30-100 microM). 7. omega-Conotoxin GVIA, a marine neurotoxin, which depressed whole cell calcium currents recorded from cultured rat parasympathetic cardiac neurones (up to 90% block at 10 nM), was ineffective at blocking synaptic transmission in submandibular ganglia (0.1-1 microM). 8. The differential effects of these calcium channel antagonists upon synaptic transmission in rat parasympathetic ganglia, suggest that either more than one type of calcium channel may be involved in transmitter release, or that the presynaptic calcium channels possess pharmacological sensitivities different from those of channel types described in ne
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PMID:Inhibition of neurally-evoked transmitter release by calcium channel antagonists in rat parasympathetic ganglia. 257 81

A 30 day exposure of C. punctatus to sublethal levels of phenol, ammonia, mercuric chloride, cadmium chloride and a mixture of the four resulted in an overall activation of guaiacol peroxidase and depression of iodide peroxidase (IPOD) activity and blood T4 titre. Interestingly enough, in case of 15 day ammonia and 1 day mercury exposures, an increase of IPOD activity was accompanied by a decrease in T4 titre. In general, phenol, mercury, cadmium and the mixture of pollutants were found to inhibit LP activity by 56% to 85% while ammonia inhibited lysosomal protease (LP) activity by 70%. Alterations in acid phosphatase (AP) activity indicate changes in the lysosomal membrane characteristics caused by these toxicants. Considering the concomitant alterations in IPOD, T4, LP and AP it is surmised that thyroid function in C. punctatus is influenced by the pollutants by two pathways, one via IPOD pathway affecting T4 synthesis and the other via lysosomal pathway affecting T4 release.
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PMID:Influence of industrial pollutants on thyroid function in Channa punctatus (Bloch). 260 23

The effects on isometric tension of three divalent ions that block calcium channels, magnesium, cobalt, and cadmium, were tested in small bundles of rat soleus fibers. Cobalt, at a concentration of 2 or 6 mM, reversibly depressed twitch and tetanic tension and the depression was much greater in solutions containing no added calcium ions. Magnesium caused much less depression of tension than cobalt. The depression of tension was not accompanied by membrane depolarization or a reduction in the amplitude of action potentials. A reduction caused by 6 mM cobalt in the amplitude of 40 or 80 mM potassium contractures was not accompanied by a comparable reduction in tension during 200 mM potassium contractures, and could be explained by a shift in the potassium contracture tension-voltage curve to more positive potentials (by +7 mV on average). Similar effects were not seen with 2 or 6 mM magnesium. At a concentration of 20 mM, both cobalt and magnesium depressed twitch and tetanic tension, cobalt having greater effect than magnesium. Both ions shifted the potassium contracture tension-voltage curve to the right by +5 to +10 mV, caused a small depression of maximum tension, and slowed the time course of potassium contractures. Cadmium (3 mM) depressed twitch, tetanic, and potassium contracture tension by more than 6 mM cobalt, but experiments were complicated by the gradual appearance of large contractures that became even larger, and sometimes oscillatory, when the solution containing cadmium was washed out. It was concluded that divalent cations affect both activation and inactivation of tension in a manner that cannot be completely explained by a change in surface charge.
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PMID:Effects of cobalt, magnesium, and cadmium on contraction of rat soleus muscle. 275 79

Young adult rats absorbed 50 p.p.m. Cd2+ added to drinking water. After 6 weeks, 3, 6 and 9 months of treatment, the ultrastructural condition of liver, kidney and muscle was observed by electron microscopy. The choice of these tissues was determined by their differences in the capacity to accumulate Cd2+: the liver is able to concentrate a considerable amount of metal, but redistributes it throughout the entire organism, while the kidney collects it in view of its elimination. Muscle contains the least Cd2+. A general regression in mitochondria cristae accompanied by a vesiculation and a fragmentation of endoplasmic reticulum appeared simultaneously in the three tissues, at as early as 6 weeks of treatment, and extended progressively with its continuation supporting evidence of a general attack of the intracellular membrane systems. Cd2+ stimulation of membrane-degrading enzymes such as phospholipases and proteases was suggested. A concomitant diminution in glycogen stores was noted. Active synthesis of neutral lipids, especially cholesterol esters, took place in liver mitochondria of treated rats in collaboration with rough endoplasmic reticulum, and progressively generated a multiplication of electron-transparent inclusions in cytoplasm. Isolated mitochondria from liver, kidney and muscle of Cd2+-treated rats maintained partial energy coupling, but displayed a rapid early fall in cytochrome oxidase followed by a partial restoration after 6 months of treatment, and a progressively slackening of succinate dehydrogenase. Isolated vesicles of liver mitochondria inner membrane of treated rats behaved as intact mitochondria, indicating changes inside the membrane itself. Addition in vitro of the metal ion to mitochondria and also to inner membrane vesicles isolated from control rats revealed that Cd2+ was able to stop completely succinate dehydrogenase, but was totally ineffective on cytochrome oxidase. Membrane fixation of Cd2+ on the flavoprotein or SH associated with succinate dehydrogenase is proposed. Considering the close parallelism of the extensive depression of microsomal NADPH cytochrome c reductase and the rapid fall in mitochondrial cytochrome oxidase, it is suggested that an indirect inhibition process occurs, through Cd2+-induced diminution of a constituent common to all cytochromes in the cell.
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PMID:Mitochondria alterations in Cd2+-treated rats: general regression of inner membrane cristae and electron transport impairment. 293 99

To investigate the relationship between left ventricular function and electrical changes during myocardial ischemia, ambulatory left ventricular function monitoring and ECG recording were made during the ergometer exercise test in 14 patients with coronary artery disease. An ambulatory ventricular function monitor consists of a small cadmium telluride (CdTe) radionuclide probe (250 g) affixed to the patient's chest wall, a preamplifer (10 g), and a portable data acquisition unit (600 g). Left ventricular time-activity curves were recorded continuously using this monitor, and the end-systolic count (volume), end-diastolic count (volume) and ejection fraction were calculated after background subtraction. Twenty-eight exercise tests were performed in the supine and upright positions. In 15 tests, left ventricular dysfunction, i.e., an increase in the end-systolic count (greater than or equal to 10%) and a decrease in ejection fraction (greater than or equal to 5%), and ST depression (greater than or equal to 0.1 mV) were observed. In these 15 tests, exercise duration was 362 +/- 27 sec. Left ventricular dysfunction occurred earlier than ST depression and the time difference was 97 +/- 19 sec. Left ventricular function recovered 33 +/- 8.5 sec after discontinuation of exercise, while ST depression continued for the additional 85 +/- 18.5 sec after recovery of left ventricular function. In conclusion, 1) left ventricular dysfunction occurs earlier than electrical changes during exercise-induced ischemia; 2) left ventricular dysfunction improves earlier than electrical changes after exercise; and 3) the same temporal sequence exists in the restoration from myocardial ischemia.
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PMID:Sequence of mechanical and electrical changes during myocardial ischemia: assessment by an ambulatory left ventricular function monitor. 326 33


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