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)

Changes in the strength of recurrent inhibition in the feline cortex in cobalt (CoCl2)-induced epilepsy were observed. The strength of inhibition was analyzed in terms of paired-pulse depression of the amplitude of somatosensory evoked potentials (SEPs) elicited by stimulation of the ventral posterolateral (VPL) thalamic nucleus. An enhancement in recurrent inhibition was observed shortly after CoCl2 application. The size of the amplitude of cortical evoked potentials (EPs) elicited by VPL stimulation increased simultaneously. The reduction of inhibition that appeared later was associated with afterdischarges (ADs) evoked by VPL stimulation. These ADs frequently extended to epileptic discharges. These results suggest that the reduction in recurrent inhibition induced by CoCl2 application plays an important role in the spread of seizure activity.
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PMID:Changes in the strength of recurrent inhibition in cobalt-induced epilepsy. 159 15

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.
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PMID:Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line. 179 58

The effect on the afferent synaptic transmission of Ba2+, Sr2+, tetraethylammonium (TEA) and 4-aminopyridine (4-AP) has been investigated in the isolated frog labyrinth by intracellularly recording the posterior canal resting and evoked receptor discharge. BaCl2 (0.3 mM) or SrCl2 (1.8 mM) substitution for normal external CaCl2 restored the afferent activity without affecting the membrane potential of the sensory fibres. On further increasing Ba2+ concentration (0.5-5 mM) a dose-dependent increase in the EPSP and spike discharges was observed in all the units examined. Ba2+ (1.8-4 mM) removed the depression of the sensory activity operated by CoCl2 (3 mM), while its facilitatory effect was completely antagonized by raising Ca2+ concentration (up to 10 mM). TEA (20 mM) elicited a clear-cut increase in the EPSP and spike discharges which, however, was less consistent than that produced by Ba2+ (1 mM). The increment in spike frequency produced by TEA and Ba2+ proved to be inversely related to the initial resting firing level of the different units. The 4-AP (4-20 mM) effect resulted in a decrease of the sensory activity, which was fully restored by TEA or Ba2+. In normal saline a linear relationship was found between the mean unit resting discharge and the respective excitatory peak response during sinusoidal rotation (0.1-0.3 Hz). This result suggest that the mechanical response is mainly determined by the unit resting level. Consistent evoked responses were obtained under TEA and Ba2+ treatment which proved to depend linearly on the new mean resting discharge of the different units. Conversely, a reduced evoked response was invariably observed in all the fibres tested in the presence of 4-AP. The present results suggest that Ba2+ and Sr2+ may substitute for Ca2+ in the transmitter release process at the cyto-neural junction, the ability of Ba2+ being even larger than that of Sr2+ and Ca2+ itself. The effects of TEA and 4-AP are discussed in the light of their possible interaction with the presynaptic K+-currents recently described in hair cells.
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PMID:The effect of barium and some channel blockers on sensory discharge of the frog labyrinth posterior canal recorded at rest and during rotation. 245 27

The protective effect of SKF 525-A on the suppression of cytochrome P-450 content and monooxygenase activities by treatment with CoCl2 and polyriboinosinic acid-polyribocytidylic acid [poly(I.C] was compared as a part of studies of suppression of drug metabolizing enzymes by interferon inducers. Induction of heme oxygenase activity by CoCl2 and poly (I.C) was not altered by simultaneous treatment with SKF 525-A. Depression of cytochrome P-450 content and benzphetamine N-demethylase activity by treatment with CoCl2 was prevented by co-treatment with SKF 525-A. This effect was explained by the prevention of release of heme from cytochrome P-450 by forming metabolic intermediate complexes with metabolites of SKF 525-A. On the other hand, poly(I.C) significantly suppressed P-450 content and benzphetamine N-demethylase and benzo [a] pyrene hydroxylase activities, even under simultaneous treatment with SKF 525-A. This inhibition by poly (I.C) was accompanied by weak staining of proteins corresponding to cytochrome P-450 in SDS gel electrophoresis. In addition, the activity of non-heme enzyme, 4-hydroxybiphenyl glucuronyltransferase, was suppressed by treatment with poly (I.C) but not by CoCl2-treatment. These findings strongly suggested that, unlike CoCl2, poly (I.C) suppressed cytochrome P-450 content and monooxygenase activities due to decreased synthesis or increased degradation of the apoprotein of cytochrome P-450 with slight contribution of the induced heme oxygenase.
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PMID:Effect of co-administration of interferon inducer, polyriboinosinic acid-polyribocytidylic acid, with SKF 525-A on hepatic drug metabolizing enzymes of rats. 309 97

A coincubation system composed of hepatocytes in primary monolayer culture and erythrocytes suspended in the culture medium was developed and used as a model for investigations of mechanisms of cyanide antidote action at the cellular level. Hepatocyte ATP was used as the cytotoxicity indicator. Treatment of rat hepatocytes in the coincubation system with KCN (1.0 mM) for 10 min at 37 degrees C selectively reduced hepatocyte ATP levels to 33 +/- 15% of control (no KCN added) levels. 4-dimethylaminophenol (DMAP), cobalt(II) chloride, sodium nitrite, sodium thiosulfate, or a combination of the last two antidotes added to the KCN-containing medium significantly reversed ATP depression and the response was concentration dependent. The relative effectiveness, on a molar basis, was estimated to be DMAP greater than CoCl2 much greater than NaNO2 congruent to Na2S2O3. NaNO2 and DMAP induced methemoglobin formation in the absence of cyanide and cyanmethemoglobin formation in its presence; erythrocytes were required in the medium for effectiveness. CoCl2 produced neither cyanmethemoglobin nor thiocyanate in appreciable quantities nor required erythrocytes for antagonism. Na2S2O3 converted cyanide to thiocyanate and reversed ATP depression without erythrocytes in the medium. The addition of erythrocytes increased these rates significantly and to a greater extent than albumin. The overall results are consistent with previously proposed modes of action for these antidotes. However, the enhancement in cyanide metabolism and ATP recovery with Na2S2O3 and erythrocytes in the system was unexpected and raises the possibility that erythrocytes may contribute to cyanide disposition and antagonism in vivo when this antidote is administered.
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PMID:Application of a hepatocyte-erythrocyte coincubation system to studies of cyanide antidotal mechanisms. 356 31

1. alpha 1-Adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The alpha 1-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101. 2. Under voltage clamp, alpha 1-adrenoceptor agonists caused an inward current at -60 mV, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the alpha 1-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of alpha 1-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by alpha 1-adrenoceptor agonists, whereas nifedipine and omega-conous toxin had no effect. In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA) did not inhibit the inward current. 3. The alpha 1-induced depolarization was blocked (or occluded) by the inclusion of GTP-gamma-S (100 microM) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late component of the after-hyperpolarization (late-AHP) that followed a single action potential. The alpha 1-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization induced by alpha 1-agonists was not changed; however, the late-AHP was reduced in duration and the alpha 1-receptor-mediated augmentation of the late-AHP was decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alpha 1-adrenoceptors in rat dorsal raphe neurons: regulation of two potassium conductances. 752 47