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)

We have demonstrated by autoradiography, displaceable binding for [125I]endothelin-1 ([125I]ET-1), [125I]endothelin-2 ([125I]ET-2), and [125I]endothelin-3 ([125I]ET-3) in the cat carotid bifurcation as well as in the nucleus of the tractus solitarius, where baroreceptor and chemoreceptor afferents from the carotid body and sinus terminate. There was also significant binding in the nodose and superior cervical ganglia. Barosensory and chemosensory discharge was recorded from filaments of the carotid sinus nerve in cats anesthetized with pentobarbitone. Intra-carotid injection of ET-1 or ET-3 (4-402 pmoles) caused transient dose-related depression of baroreceptor discharge without any immediate effects on systemic blood pressure (BP) or heart rate; there was a delayed biphasic effect on BP. ET-1 had little effect on chemosensory discharge during the first 15 s post-injection, but there was a delayed (45-90 s) dose-related increase in discharge. The effects of all three ETs were qualitatively similar, and ET enhanced chemoexcitation evoked by either acetylcholine or sodium cyanide. Our results show that (a) ET binding sites are located in the baroreceptor and chemoreceptor afferent pathways and (b) ETs can influence afferent activity of baroreceptors and chemoreceptors. Further studies are needed to determine the significance of these findings, particularly with regard to reflex control of the cardiovascular system.
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PMID:Localization of [125I]endothelin binding sites in the region of the carotid bifurcation and brainstem of the cat: possible baro- and chemoreceptor involvement. 172 86

Measurements of the intracellular free concentration of Ca2+ ([Ca2+]i) were performed during fatiguing stimulation of intact, single muscle fibers, which were dissected from a mouse foot muscle and loaded with fura-2. Fatigue, which was produced by repeated 100-Hz tetani, generally occurred in three phases. Initially, tension declined rapidly to approximately 90% of the original tension (0.9 Po) and during this period the tetanic [Ca2+]i increased significantly (phase 1). Then followed a lengthy period of almost stable tension production and tetanic [Ca2+]i (phase 2). Finally, both the tetanic [Ca2+]i and tension fell relatively fast (phase 3). The resting [Ca2+]i rose continuously throughout the stimulation period. A 10-s rest period during phase 3 resulted in a significant increase of both tetanic [Ca2+]i and tension, whereas a 10-s pause during phase 2 did not have any marked effect. Application of caffeine under control conditions and early during phase 2 resulted in a substantial increase of the tetanic [Ca2+]i but no marked tension increase, whereas caffeine applied at the end of fatiguing stimulation (tension depressed to approximately 0.3 Po) gave a marked increase of both tetanic [Ca2+]i and tension. The tetanic [Ca2+]i for a given tension was generally higher during fatiguing stimulation than under control conditions. Fatigue developed more rapidly in fibers exposed to cyanide. In these fibers there was no increase of tetanic [Ca2+]i during phase 1 and the increase of the resting [Ca2+]i during fatiguing stimulation was markedly larger. The present results indicate that fatigue produced by repeated tetani is caused by a combination of reduced maximum tension-generating capacity, reduced myofibrillar Ca2+ sensitivity, and reduced Ca2+ release from the sarcoplasmic reticulum. The depression of maximum tension-generating capacity develops early during fatiguing stimulation and it is of greatest importance for the force decline at early stages of fatigue. As fatigue gets more severe, reduced Ca2+ sensitivity and reduced Ca2+ release become quantitatively more important for the tension decline.
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PMID:Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers. 176 71

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

Cyanide is known to initiate release of catecholamines from chromaffin cells and isolated adrenals but the effect of cyanide on plasma catecholamine levels has not been reported. The present study demonstrates that cyanide produces marked elevation of plasma catecholamines in mice. A sublethal dose of KCN (5 mg/kg, sc) significantly increased plasma norepinephrine (NE) and epinephrine (EPI) at 5 min after administration, and the elevated levels returned to normal at 15 min. At a dose of 10 mg/kg, NE and EPI plasma levels remained elevated over a 15 min period. Multiple exposures to sublethal doses of KCN (5 mg/kg, sc, 4 doses at 15 min intervals) produced a steep, sustained rise in plasma NE and EPI. Administration of KCN (15.6 micrograms) directly into the lateral ventricles of the brain caused convulsions and respiratory depression, but did not affect plasma catecholamine levels. Pretreatment with pargyline did not alter the magnitude of the response to KCN. Adrenalectomy prevented the increase in plasma EPI and had no influence on plasma NE levels, indicating cyanide acts directly on the adrenals to stimulate EPI release. It is proposed that KCN directly stimulates the sympathoadrenal axis to increase plasma catecholamine levels.
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PMID:Cyanide-induced increases in plasma catecholamines: relationship to acute toxicity. 179 1

1. The effects of complete metabolic inhibition on excitation-contraction coupling in heart were studied by exposing patch-clamped guinea-pig ventricular myocytes, loaded via the patch pipette with the Ca2+ indicator Fura-2 (0.1 mM), to carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP, 1 microM) and 2-deoxyglucose (2-DG, 10 mM) while simultaneously recording membrane current, Fura-2 fluorescence, and cell motion. The patch pipette solution contained Cs+ and TEA (tetraethylammonium) to partially block K+ currents. 2. During voltage clamps from a holding potential of -40 mV to a test potential of 0 mV, complete metabolic inhibition decreased the Ca2+ current (ICa), activated the ATP-sensitive K+ current, modestly elevated diastolic [Ca2+]i and markedly reduced the [Ca2+]i transient without altering its voltage dependence. Active shortening was impaired and diastolic cell length decreased prior to large increases in diastolic [Ca2+]i, consistent with rigor induced by ATP depletion. Return of the [Ca2+]i transient to baseline and relaxation upon repolarization were also delayed. 3. Despite the depression of the peak [Ca2+]i transient induced by membrane depolarization during metabolic inhibition, the [Ca2+]i transient induced by a rapid exposure to 5 mM-caffeine was greater than control. The Na(+)-Ca2+ exchange current during the caffeine-induced [Ca2+]i transient was not affected by metabolic inhibition. 4. [Ca2+]i transients depressed by metabolic inhibition could be enhanced by augmenting ICa with elevated [Ca2+]o (10 mM) and Bay K 8644 (5 microM). 5. To study the relationship between the magnitude of ICa and the amplitude of the [Ca2+]i transient, ICa was modulated either by (a) voltage clamping the cell to different membrane potentials at constant [Ca2+]o or by (b) rapidly altering [Ca2+]o immediately prior to a voltage clamp to a fixed membrane potential. Under control conditions, the relationship between the size of ICa and the magnitude of the [Ca2+]i transient was the same whether ICa was modulated by altering membrane potential or [Ca2+]o, suggesting that membrane potential does not significantly modulate the Ca(2+)-induced Ca2+ release mechanism of cardiac excitation-contraction coupling. 6. After metabolic inhibition, however, the same ICa released less Ca2+ than under control conditions, consistent with some impairment of the Ca2+ release mechanism. 7. These results suggest that under conditions in which excitability is maintained by controlling membrane voltage and minimizing metabolically sensitive K+ currents, the decreased [Ca2+]i transient observed during metabolic inhibition severe enough to induce rigor is caused primarily by depression of ICa and not by depletion of intracellular Ca2+ stores. Additional factors also modestly hinder Ca2+ release from intracellular stores during metabolic inhibition.
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PMID:Mechanisms of excitation-contraction coupling failure during metabolic inhibition in guinea-pig ventricular myocytes. 182 31

Addition of bovine serum albumin to state 4 mitochondria results in a depression of the proton leak and of the resting respiration of 70 and 25%, respectively. The conductance membrane potential diagram, both in the ohmic and in the non-ohmic region, shows that in the presence of bovine serum albumin the level of ohmic conductance is lowered while that of non-ohmic conductance is increased toward higher delta psi values. The same effect is observed during operation of the different proton pumps. Addition of chloroform affects the conductance membrane potential diagram in the following manner: there is no effect in the ohmic region with all pumps, while there is an effect in the non-ohmic region either at site III or at sites II plus III but not at site II. This suggests a possible effect of chloroform at the level of the cytochrome oxidase proton pump. During titration with oligomycin of the ATPase proton pump the conductance potential diagram shows a region of non-ohmicity only in the presence but not in the absence of an ATP-regenerating system. Protonophoric uncouplers such as carbonyl cyanide p(trifluoromethoxy)phenylhydrazone and intrinsic uncouplers such as chloroform have different effects on the relationship between rates of charge translocation and of oxygen consumption, and thus on the pump stoichiometries, in that the slope of the diagram is modified by the latter but not by the former. The differential effects of protonophores and of intrinsic uncouplers on the stoichiometries have been analyzed by computer simulations and represent an additional criterion to distinguish between extrinsic and intrinsic mechanisms of uncoupling.
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PMID:Flux ratios and pump stoichiometries at sites II and III in liver mitochondria. Effect of slips and leaks. 184 85

Several studies have demonstrated that focal mechanisms contribute to arrhythmogenesis during acute myocardial ischemia in vivo. However, the biochemical derangements during ischemia may either potentiate or depress the electrophysiological mechanisms leading to focal arrhythmias. In the study presented here we have characterized the consequences of various levels of cellular depression and of alterations in the extracellular environment on the development of early (EADs) and delayed (DADs) afterdepolarizations induced by catecholamines. Adult canine myocytes were exposed to: normoxia; hypoxia (pO2 less than 10 mmHg); hypoxia + high K+ or cyanide infusion. Early and delayed afterdepolarizations were induced by alpha or beta adrenergic stimulation in the different experimental conditions by infusing isoproterenol (10(-8)-10(-6) M) or phenylephrine (10(-7)-10(-5) M) + the betablocker nadolol. Hypoxia did not modify EADs or DADs induced by beta stimulation and potentiated DADs induced by alpha stimulation; hypoxia + high K+ blunted DADs induced by both types of stimulation and cyanide infusion completely prevented and suppressed them. Thus, triggered arrhythmias dependent upon adrenergic stimulation can either be potentiated or inhibited by the biochemical derangements of acute ischemia. Focal arrhythmias are more likely to occur in the borderline ischemic cells where cellular depression and extracellular K+ accumulation are less marked.
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PMID:[Variations in arrhythmogenic response to catecholamines in acute myocardial ischemia]. 191 17

Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities.
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PMID:Toxicological findings in Federal Aviation Administration general aviation accidents. 191 71

Chemical control of respiration in cats after chronic normobaric hyperoxia (NH; inhalation of 100% O2 for 60-67 h) was compared with that of control rats, anesthetized with pentobarbital. After chronic hyperoxia, induction of moderate hypoxia (PaO2 = 50-60 Torr) increased inspiratory time (TI) often without increasing tidal volume (VT). More intense hypoxia (PaO2 = 40-50 Torr) depressed tidal volume and further increased TI, diminishing the respiratory drive (VT/TI). Hypercapnia, on the other hand, increased tidal volume and shortened respiratory cycle time; but these responses were subnormal. The normal stimulatory effects of intravenous nicotine and inhibitory effect of dopamine on carotid chemo-receptor activity and ventilation were preserved in the NH cats. Cyanide, however, did not stimulate carotid chemoreceptor activity and ventilation. Thus, the changes in the carotid and aortic chemosensory activities elicited appropriate reflex ventilation responses, indicating that the central component of the chemoreflex was not impaired. The ventilatory depression during hypoxia despite an active chemosensory input is consistent with the lack of carotid chemosensory response to and a central depressant effect of hypoxia in the NH cats, and was presumably associated in part with an increased responsiveness of airway reflexes. We conclude that chronic hyperoxia selectively attenuated carotid chemosensory and chemoreflex responses to hypoxia.
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PMID:Chemical respiratory control in chronically hyperoxic cats. 207 96

1. The carotid body chemoreceptors are stimulated in situ by hypoxia. We have studied type I cells freshly dissociated from the carotid body of the rabbit. We have used microfluorimetric and patch clamp techniques to examine the responses to hypoxia, to anoxia, and to metabolic inhibition. 2. NADH autofluorescence measured at both 400 and 500 nm increased rapidly and reversibly in response to anoxia or to cyanide (CN-), reflecting a change in mitochondrial metabolism. 3. Indo-1 was used to measure changes in intracellular calcium, [Ca2+]i. Anoxia reversibly increased [Ca2+]i from approximately 50-100 to approximately 200-450 nM in all cells tested. The response showed a striking temperature sensitivity. Responses to hypoxic stimuli were barely detectable at 17-20 degrees C, and were dramatically increased on warming to 36 degrees C. In contrast, responses to K(+)-induced depolarization were only slightly increased in rate of onset and recovery by warming. 4. The rise in [Ca2+]i originated largely from an intracellular store which was slowly depleted by exposure to nominally Ca2(+)-free solutions. Responses were unaffected by blockade of Ca2+ channels with organic (D600, verapamil) or inorganic (Co2+) blockers, by blockade of Na+ channels with tetrodotoxin (TTX), or by increasing action potential duration with tetraethylammonium (TEA). Responses to anoxia were increased by the increased [Ca2+]i loading that follows prior exposure to Ca2(+)-free solutions. 5. Responses to anoxia, to blockade of electron transport by CN-, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP), were equivalent in amplitude. The response to anoxia was occluded by concurrent application of FCCP, suggesting that the Ca2+ originates from the same pool in each case. 6. At 35-36 degrees C, responses to graded levels of PO2 were also graded. Thresholds varied between cells, but were typically 30-50 mmHg. Stimulus-responses curves were essentially hyperbolic, increasing dramatically as the PO2 approached 0 mmHg. 7. The sensitivity of cells to hypoxic solutions was increased by acidification of the superfusate over the pH range from 7.3 to 6.85. 8. Cell-attached patch clamp recordings showed depression of spontaneous action potentials associated with a rise in [Ca2+]i during exposure to anoxic solutions. Whole-cell recordings showed that anoxia increased a voltage-gated gK as described previously for CN-, while producing no change in resting conductance. 9. These data suggest that the rise in [Ca2+]i originates largely from Ca2+ efflux from a mitochondrial pool.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Responses of type I cells dissociated from the rabbit carotid body to hypoxia. 223 19

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