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)

Intracellular current-clamp and single-electrode voltage-clamp techniques were used to study in vitro action potentials and the action of vasoactive intestinal contractor (VIC; 0.03-1 microM) on the high-voltage-activated Ca2+ currents (ICa) of neurons in feline colonic parasympathetic ganglia. In the current-clamp recording mode, action potential amplitude was depressed by cobalt (1 mM) and omega-conotoxin (300 nM) or in nominally Ca(2+)-free Krebs solutions. In the single-electrode voltage-clamp recording mode, the ICa was isolated by blocking the voltage-gated Na+ current with tetrodotoxin (1-3 microM) and by Krebs solutions containing a low Na+ concentration. The voltage-activated K+ currents were blocked by intracellular injection of cesium through a recording electrode filled with 2 M CsCl and external application of tetraethylammonium (30-50 mM) and barium (2 mM). The Ca(2+)-dependent Cl- current was blocked by replacement of Ca2+ (2 mM) with equimolar barium. Anomalous rectification was blocked by external application of 2 mM cesium. The ICa was evoked by depolarizing step commands more positive than -40 mV from holding potentials ranging between -80 and -60 mV. ICa was depressed by cobalt (1 mM), cadmium (100 microM), and omega-conotoxin (500 nM) but not by nifedipine (10 microM), nicardipine (10 microM), and verapamil (10 microM). BAY K 8644 (3-10 microM) also did not affect the ICa. VIC (0.1-1 microM), one of the endothelin (ET) isopeptides, caused an inward current followed by an outward current. The VIC-induced inward and outward currents were associated with an increase and decrease in membrane conductance, respectively. VIC also caused an initial depression followed by a long-lasting augmentation of the ICa. ET-1, ET-2, and ET-3 equally mimicked the action of VIC on both holding current and ICa. These data suggest that VIC activates a receptor-operated channel and modulates the omega-conotoxin-sensitive voltage-activated Ca2+ channels through ETB receptor subtypes of neurons in feline colonic parasympathetic ganglia.
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PMID:Effects of vasoactive intestinal contractor on voltage-activated Ca2+ currents in feline parasympathetic neurons. 827 67

In the CA1 region of rat hippocampal slices, spreading depression (SD) was provoked by a brief period of hypoxia or by localized application of high potassium solution. We measured extracellular DC voltage (Vo), extracellular potassium concentration ([K+]o) and/or extracellular Ca2+ concentration ([Ca2+]o). SD was provoked under control conditions and also when voltage-gated Ca2+ channels were blocked by application of 2 mM Ni2+ or Co2+. In some experiments, CPP, DNQX, or the two together were also applied to block glutamate receptor-coupled channels. When SD was provoked by hypoxia, these treatments significantly increased the latency of SD onset and decreased the amplitudes of the accompanying delta Vo, delta [Ca2+]o and delta [K+]o. Hypoxia-induced SD was never blocked completely, however and delta [Ca2+]o was reduced at most by 50%. When SD was provoked by application of high K+ solution near the recording site, Ni2+ or Co2+ partially suppressed the Vo and [Ca2+]o shifts but did not block SD altogether. When high K+ solution was applied at a distance, Ni2+ or Co2+ blocked the propagation of SD to the recording site. We conclude that during SD, a significant proportion of the calcium ions flowing into neurons does not pass through voltage-gated or glutamate receptor-linked channels.
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PMID:Role of calcium channels in spreading depression in rat hippocampal slices. 838 11

Effects of glutamate and agonists (aspartate, NMDA, quisqualate, AMPA, kainate) on dorsal root and reticulomotoneuronal excitatory postsynaptic potentials (EPSPs), as well as on spontaneous postsynaptic potentials (PSP), were studied in the motoneurons of isolated frog spinal cord. Depolarizing responses were evoked by glutamate or agonists bath application. Amplitude of the response decreased in conditions of TTX-block or replacement of Ca2+ by Mn2+, Mg2+ or Co2+ in perfusing solution. Excitatory amino acid antagonists (kynurenate, CNQX, APV, argiopine) also reduced depolarizing response amplitude. DR and RF EPSPs significantly increased in amplitude (and spontaneous PSP in amplitude and frequency) during depolarization, evoked by glutamate or agonists. The potentiation reached up to 300 %. Potentiation diminished with depolarization decay. Sometimes several minutes depression of EPSPs was observed after the depolarizing response. There was no potentiation of the spontaneous PSPs in conditions of TTX-block or replacement of Ca2+ by Mn2+ in perfusing solution. The data obtained suggest rather presynaptic, than postsynaptic mechanism of the potentiation. We found no depressant effect of glutamate or agonists on postsynaptic glutamate receptors, at least for 10 minutes contact. Effects of more prolonged applications and some changes of EPSP amplitude after depolarizing response appear to be associated with other types of glutamate receptors.
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PMID:[The potentiation of postsynaptic potentials under the influence of glutamate and agonists in the motoneurons of the frog Rana ridibunda]. 877 84

The cobalt model of epilepsy, in combination with the C-14 2-deoxyglucose (2-DG) autoradiographic technique, was used to assess the effects of phenytoin (PHT) and ethosuximide (ESM), two antiepileptic drugs, and ketamine (KET), a drug with anticonvulsant properties, on brain activity. Nine days after the unilateral insertion of a cobalt rod into visual cortex, the nondrugged control rats showed the usual hypermetabolic regions of putative epileptogenic tissue both adjacent to the necrotic cortical cobalt rod implant zone and more distally in the connecting thalamus. PHT and ESM, given a single injections immediately before the 2-DG uptake and clearing period, diminished glucose uptake in the cobalt-induced hypermetabolic "patches" as well as in normal tissue. However, both drugs decreased 2-DG uptake more in the thalamic patches, than in the less hypermetabolic cortical patches, where the drug-induced depression in glucose metabolism was the same as for normal tissue. These findings suggest that PHT and ESM, regardless of their actions on cell receptors and membrane conductances, are ultimately of therapeutic value because more active nervous tissue (such as epileptic tissue) is more vulnerable to the depressing effects of these drugs than is less active tissue. KET, in contrast to PHT and ESM, did not depress metabolic activity throughout the brain generally and even clearly increased it in limbic system structures. Also in contrast to PHT and SEM, KET diminished activity in the cobalt-induced patches without reducing it in the normal tissue of the homotopic control regions. The more selective depressing action of KET, an N-methyl-D-aspartate (NMDA) antagonist, may be related to the role NMDA receptors play in supporting strong nervous activity. The discussion emphasizes the usefulness of a combined cobalt/2-DG approach to antiepileptic drug assessment.
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PMID:A combined cobalt and C-14 2-deoxyglucose approach to antiepileptic drug assessment. 882 60

Amphiphilic lipid metabolites, including lysophosphatidylcholine (lysoPC) and long-chain acylcarnitine, accumulate in an ischemic myocardium and exert deleterious effects on membrane function. The effects of short-chain (3-carbon-chain, C3), medium-chain (C6 and C8), long-chain (C16) acylcarnitines, and lysoPC on the sodium current (INa) of isolated guinea-pig ventricular cells and on membrane fluidity and [14C]lysoPC uptake in cultured mouse embryo ventricular cells were examined. Guinea-pig ventricular cells were superfused with low-Na+(60 mM) Tyrode solution at a temperature of 32-33 degrees C. Ca2+ and K+ currents were blocked by external Co2+(3 mM) and internal Cs+(140 mM), respectively. Neither propionylcarnitine (PpC, C1) nor hexanoylcarnitine (HxoC. C6) at concentrations of 50, 100, 500 microM affected the amplitude of peak LNa, evoked by depolarizing pulses (0.5 Hz) to -20 mV from a holding potential of -100 mV. Octanoylcarnitine (OcoC, C8) (50 and 100 microM) did not alter the amplitude of peak INa while the highest concentration (500 microM) did inhibit it by 7.7 +/- 3.0% (mean +/- S.E., n = 6) significantly. Palmitoylcarnitine (PamC, C16) (1, 5, and 50 microM), decreased the amplitude of peak INa by 16.6 +/- 5.2% (n = 5), 36.1 +/- 4.3% (n = 11), and 52.7 +/- 8.8% (n = 4), respectively. LysoPC (50 microM) irreversibly depressed INa within 30 +/- 4 seconds (n = 4), and cell contracture occurred. If short- and medium-chain acylcarnitines would prevent the depressant effects of lysoPC on INa was then investigated. In the presence of PpC (100 microM) or HxoC (100 microM), the effects of lysoPC (either depression of INa or development of cell contracture) were not observed, while OcoC (100 microM) did not prevent any of these effects of lysoPC. In contrast, PpC and HxoC failed to prevent the reduction of INa caused by PamC. From these findings and membrane fluidity and [14C]lysoPC uptake studies, it was concluded that PpC exerts the protective effect by preventing the incorporation of lysoPC into phospholipid bilayers, and that short-chain acylcarnitine has a potent anti-amphiphilic effect against the amphipathic insults caused by lysoPC, whereas long-chain acylcarnitine had a potent amphiphilic effect; medium-chain acylcarnitine appeared to share both characteristics.
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PMID:Hydrocarbon chain length-dependent antagonism of acylcarnitines to the depressant effect of lysophosphatidylcholine on cardiac sodium current. 893 Aug 13

Telomere repeat sequence (TRS) DNA is found at the termini of most eukaryotic chromosomes. The sequences are highly repetitive and G-rich (e.g., [C(1-3)A/TG(1-3)]n for the yeast Saccharomyces cerevisiae) and are packaged into nonnucleosomal protein-DNA structures in vivo. We have used total intensity light scattering and electron microscopy to monitor the effects of yeast TRS inserts on in vitro DNA condensation by cobalt (III) hexaammine. Insertion of 72 bp of TRS into a 3.3-kb plasmid depresses condensation as seen by light scattering and results in a 22% decrease in condensate thickness as measured by electron microscopy. Analysis of toroidal condensate dimensions suggests that the growth stages of condensation are inhibited by the presence of a TRS insert. The depression in total light scattering intensity is greater when the plasmid is linearized with the TRS at an end (39-49%) than when linearized with the TRS in the interior (18-22%). Circular dichroism of a 95-bp fragment containing the TRS insert gives a spectrum that is intermediate between the A-form and B-form, and the anomalous condensation behavior of the TRS suggests a noncanonical DNA structure. We speculate that under conditions in which the plasmid DNA condenses, the telomeric insert assumes a helical geometry that is similar to the A-form and is incompatible with packing into the otherwise B-form lattice of the condensate interior.
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PMID:Insertion of telomere repeat sequence decreases plasmid DNA condensation by cobalt (III) hexaammine. 951 44

Cobalt-55 (55Co) is a positron emission tomography (PET) tracer used to demonstrate brain damage, possibly associated to calcium-mediated processes. The degree of 55Co accumulation correlates with the severity of ischaemia in stroke patients. It is still a matter of debate whether ipsilateral thalamic hypometabolism (ITH) and crossed cerebellar hypometabolism (CCH), occurring after middle cerebral artery (MCA) infarcts, represent only a metabolic depression of these remote regions or can lead to structural damage. The present study investigates whether an increased 55Co influx can be demonstrated with PET in ITH and CCH after MCA infarcts. About half of the patients with ITH and CCH had a significant degree of 55Co uptake in, respectively, the ipsilateral thalamus and the contralateral cerebellar hemisphere. It was observed in patients with severe signs of stroke on admission and poor clinical outcome, and correlated well with the degree of 55Co influx within the supratentorial infarct. The present study demonstrates that ITH and CCH after MCA infarction can represent structural damage in these remote areas that occurs during the second week after stroke onset.
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PMID:Cobalt-55 positron emission tomography of ipsilateral thalamic and crossed cerebellar hypometabolism after supratentorial ischaemic stroke. 987 61

The actions of external Cd2+ on the twitch and tetanic contractions, action potentials and potassium (K+) contractures of rat soleus muscle fibre bundles have been investigated. Cd2+ at 1-1.5 mM did not significantly alter tetanic tension, but increased twitch tension and increased the duration and overshoot of action potentials. At >/=3 mM, Cd2+ (1) depressed tetanic contractions and initially potentiated but later depressed twitches, (2) abolished the action potential overshoot, and (3) shifted peak K+ contracture tension to more positive membrane potentials. Twitch and tetanic contractions, and action potentials remained depressed when Cd2+ was washed out of the bath. The effects of Cd2+ on the twitch, tetanus and action potential were mimicked by Zn2+, while La3+ and Co2+ at 3 mM - or Mg2+ and Ca2+ at 30 mM - depressed peak twitch and tetanic tension, but did not potentiate twitches. The results suggest that: (1) Cd2+ and Zn2+ potentiate twitch tension by prolonging action potential depolarisation; (2) Cd2+ depresses twitch and tetanic tension by reducing the action potential overshoot, and causing a positive shift in the voltage dependence of contraction; and (3) the irreversible depression of action potential amplitude in rat soleus muscle is a specific property of Cd2+ and Zn2+ that is not shared by Co2+, Mg2+ or Ca2+.
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PMID:Effects of external cadmium ions on excitation-contraction coupling in rat soleus fibres. 992 59

Authors evaluated the correlation between immune system and metal ions release in blood of 17 subjects with Cr/Co/Ni joint prostheses. For the purpose Chromium (Cr), Cobalt (Co) and Nickel (Ni) serum levels were measured and, at the same time some immunological parameters (Leukocytes, Lymphocytes and Lymphocytes T, B and Natural Killer cells sub-populations) were evaluated. The results showed a significant decrease of Leukocytes, Lymphocytes and of T Lymphocytes sub-populations. At the same time it was demonstrated a significant increase of Chromium, Cobalt and Nickel levels in patients with joint prostheses as compared to control population (23 patients). In conclusion, ions release from metallic surface of the prostheses is correlated with a depression of immune system. This correlation could depend on a toxic action on immune system caused by the products released by the implant. It could also depend on a lymphocytes compartimentalization in periprosthetic tissues as a consequence of a cell-mediated hypersensitivity reaction towards implants corrosion products.
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PMID:The effects of metal corrosion debris on immune system cells. 1036 19

In Salmonella typhimurium, formation of the cobalt-carbon bond in the biosynthetic pathway for adenosylcobalamin is catalyzed by the product of the cobA gene which encodes a protein of 196 amino acid residues. This enzyme is an ATP:co(I)rrinoid adenosyltransferase which transfers an adenosyl moiety from MgATP to a broad range of co(I)rrinoid substrates that are believed to include cobinamide, its precursor cobyric acid and probably others as yet unidentified, and hydroxocobalamin. Three X-ray structures of CobA are reported here: its substrate-free form, a complex of CobA with MgATP, and a ternary complex of CobA with MgATP and hydroxycobalamin to 2.1, 1.8, and 2.1 A resolution, respectively. These structures show that the enzyme is a homodimer. In the apo structure, the polypeptide chain extends from Arg(28) to Lys(181) and consists of an alpha/beta structure built from a six-stranded parallel beta-sheet with strand order 324516. The topology of this fold is very similar to that seen in RecA protein, helicase domain, F(1)ATPase, and adenosylcobinamide kinase/adenosylcobinamide guanylyltransferase where a P-loop is located at the end of the first strand. Strikingly, the nucleotide in the MgATP.CobA complex binds to the P-loop of CobA in the opposite orientation compared to all the other nucleotide hydrolases. That is, the gamma-phosphate binds at the location normally occupied by the alpha-phosphate. The unusual orientation of the nucleotide arises because this enzyme transfers an adenosyl group rather than the gamma-phosphate. In the ternary complex, the binding site for hydroxycobalamin is located in a shallow bowl-shaped depression at the C-terminal end of the beta-sheet of one subunit; however, the active site is capped by the N-terminal helix from the symmetry-related subunit that now extends from Gln(7) to Ala(24). The lower ligand of cobalamin is well-ordered and interacts mostly with the N-terminal helix of the symmetry-related subunit. Interestingly, there are few interactions between the protein and the polar side chains of the corrin ring which accounts for the broad specificity of this enzyme. The corrin ring is oriented such that the cobalt atom is located approximately 6.1 A from C5' of the ribose and is beyond the range of nucleophilic attack. This suggests that a conformational change occurs in the ternary complex when Co(III) is reduced to Co(I).
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PMID:Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP. 1114 30


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