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)

Calcium entry into molluscan neurones during depolarizing voltage-clamp steps activates an outward current which on repolarization decays over periods of more than 30 sec. This slowly decaying tail current was used to study the relation between calcium buffering in cytoplasm and the decline of a calcium-activated membrane process. Calcium-dependent outward current was also studied after injection of calcium into the cytoplasm. The time course of the fall of outward tail current was much less sensitive than tail current amplitude to the amount of calcium entry. Increasing bath temperature from 5 to 15 degrees C decreased the rate of fall of outward tail current activated by calcium entry. In contrast, outward current activated by calcium injection declined more rapidly at higher temperatures. Injection of sufficient EGTA to give maximum depression of outward current during depolarizations reduced the amplitude of outward tail current by at most 50%. After EGTA injection outward tail current declined more rapidly immediately following repolarization, but returned to base line at about the same time as the control. After injection of EGTA, outward current activated by calcium injection was reduced or completely blocked, and returned to base line more rapidly. Application of the mitochondrial uncoupler carbonyl cyanide m-chlorophenyl hydrazone (CCCP) did not alter the decay time course of outward tail current, but markedly prolonged the decline of outward current activated by calcium injection. The slow kinetics of outward tail current were compared to predictions of the concentration of calcium ions at the outermost surface of a spherical model cell following calcium influx. We conclude that after depolarization and calcium entry, the diffusion and binding of free calcium to cytoplasmic buffers plays a key role in determining the rate of fall of outward tail current. Further, different mechanisms influence the decline of calcium-dependent outward current following injection of calcium into the cytosol.
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PMID:Calcium buffering and slow recovery kinetics of calcium-dependent outward current in molluscan neurones. 630 36

Dopamine D2-receptors were directly identified in receptor binding assays with washed particulate preparations of rabbit carotid body using the selective ligand, [3H]domperidone. High affinity, saturable specific binding of [3H]domperidone was clearly demonstrable and chronic section of the sinus nerve resulted in a 32% decrease in the labelling of the dopamine D2-sites. Adenylate cyclase activity was also detected in rabbit carotid body homogenates and although this enzyme was stimulated 4-fold by 10 mM sodium fluoride, neither dopamine nor isoprenaline significantly altered basal activity. On the other hand, in the intact carotid body incubated in vitro, 10(-5) M isoprenaline increased the basal cyclic AMP content 6-fold, though dopamine was again ineffective. The effect of various selective dopamine receptor antagonists and agonists was also studied on chemoreceptor afferent discharge. The results confirm that depression of 'spontaneous' chemosensory discharge is the predominant effect of dopamine (0.01-100 micrograms) in rabbits. The 'selective' D2-agonist, LY 141865, proved very effective (ID50 3.3 nmol) and was equipotent with dopamine (ID50 4.2), whereas, the D1-agonist, SK & F 38393, was very ineffective (ID50 150). The D2-antagonists domperidone and (-)-sulpiride produced a dose-related decrease in the chemodepressant responses to dopamine and LY 141865. However, there was no evidence for any appreciable excitatory action of either of these agonists after blockade of their chemo-depressant effects. The D2-antagonists variably affected the spontaneous activity, there being an increase in discharge on average, whereas responses to hypoxia, cyanide and CO2 were reduced. The present results from biochemical and neuropharmacological studies, provide strong evidence for the presence of functional dopamine D2-receptors in the rabbit carotid body, and suggest that the receptor involved in dopamine-induced depression of chemosensory discharge is of D2-type.
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PMID:Direct biochemical and neuropharmacological identification of dopamine D2-receptors in the rabbit carotid body. 632 Sep 58

Dopamine levels in rat carotid bodies and the effects of intravenous dopamine injections on respiration in adult rats anaesthetized with pentobarbitone have been studied in animals which were treated with capsaicin neonatally. Levels of dopamine were five fold higher in the carotid bodies of capsaicin-treated rats as compared with vehicle-treated controls, but there was no significant difference between capsaicin-treated and vehicle-treated rats in their ID50 values for dopamine-induced respiratory depression. Domperidone, a dopamine D2-receptor antagonist, substantially reduced the respiratory depression caused by dopamine, both in capsaicin-treated and in control animals, suggesting that a D2-receptor was involved in the response. Cutting the carotid sinus nerves greatly reduced the ventilatory-depressant effect of dopamine, showing that sensory receptors, most probably arterial chemoreceptors, were responsible for most of the response. Substantially less reflex hyperventilation was evoked in capsaicin-treated rats by the peripheral chemoreceptor stimulants hypoxia and sodium cyanide, in comparison with the controls, and domperidone did not increase the responsiveness. About 80% of the reflex ventilatory change originated from carotid body chemoreceptors. The hypoventilation caused by breathing 100% O2 was not significantly different in capsaicin-treated rats when compared with controls. Domperidone substantially reduced this response in capsaicin-treated rats, but not in vehicle-treated animals. Dopamine-induced respiratory depression in capsaicin-treated rats was slightly enhanced, rather than reduced, by oxygen breathing; domperidone remained an effective antagonist of dopamine-induced ventilatory depression. Most of the reduction in respiration caused by dopamine in rats anaesthetized with pentobarbitone can be attributed to actions on a dopamine D2-receptor located in the carotid body. However, despite the increased levels of dopamine found in the carotid bodies, the reduced peripheral chemosensitivity observed in anaesthetized capsaicin-treated rats does not appear to result from a change in sensitivity to dopamine.
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PMID:Changes in carotid body amine levels and effects of dopamine on respiration in rats treated neonatally with capsaicin. 651 43

The mechanism of the metabolic pathway of acrylonitrile to cyanide (and subsequently to thiocyanate which is excreted in the urine) was already previously confirmed by our work in vitro as well as in vivo. This metabolic route of AN via glycidonitrile and glycolaldehyde cyanohydrin is not the dominant pathway in the total balance of AN metabolism and does not elucidate the fate of the predominant amount of AN. By means of AN labelled with 14C on the nitrile group it was confirmed that, when different routes of administration are used, AN forms in the rat the main portion of radioactivity excreted in the urine in "non-thiocyanate" metabolites. Based on reflection on the reactivity of AN the assumption was expressed that possible metabolites of AN may be S-(2-cyanoethyl)cysteine (CEC) or N-acetyl-S-(2-cyanoethyl)cysteine (AcCEC), so called AN-mercapturic acid. Both these substances were synthetized in our laboratory and used as standards on paper chromatography of urine of animals exposed to AN. Evidence was provided that the main metabolite of AN in rats and rabbits is AcCEC. In the urine of rats 8 hours following administration of AN-14CN in addition to AcCEC another metabolite appears the structure of which was not elucidated so far. By means of preparative paper chromatography of the methylene chloride extract of rabbit urine obtained after subcutaneous injection of AN it proved possible to isolate AcCEC in the form of its dicyclohexyammonium salt. This salt did not produce a depression of the melting point with the synthetically prepared standard. This proved unequivocally the identity of the two substances.
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PMID:New findings on acrylonitrile metabolism. 722 25

We wondered if depression of oxidative adenosine triphosphate (ATP) production caused pulmonary vasoconstriction. If so, then several chemically different inhibitors of oxidative ATP production all should cause pulmonary pressor responses. The vascular reactivity of isolated, blood-perfused rat lungs was established by eliciting pressor responses to airway hypoxia and to intraarterial angiotensin II. Then, during normoxia, we added to perfusate one of five chemical inhibitors of oxidative ATP production: 10 mM azide, 1 mM cyanide, 1 mM dinitrophenol, 5 or 10 microM antimycin A, or 0.5 microM rotenone. Each of the five chemical inhibitors, but not their solvents, caused a transient pressor response, followed by loss of vascular reactivity to hypoxia, angiotensin II, and chemical inhibitors. The inhibitor pressor responses were not due to an effect on blood cells, since they also were seen in lungs perfused with plasma. The magnitudes of pressor responses to all metabolic inhibitors except azide correlated with the magnitudes of preceding pressor responses to hypoxia, but not to the preceding angiotensin II responses. When verapamil or calcium chloride was added to perfusate, the hypoxic and inhibitor pressor responses were blunted more than was the angiotensin II response. Thus, five chemically different substances, inhibiting different steps of oxidative ATP production, all caused pressor responses that were blocked readily by verapamil and by increased perfusate calcium chloride. These results support the possibility that depression of oxidative ATP production elicits pulmonary vasoconstriction that is dependent on influx of extracellular calcium. Hypoxia might also be sensed in the pulmonary circulation by decreased oxidative ATP production in some as yet unidentified lung cell.
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PMID:Inhibitors of oxidative ATP production cause transient vasoconstriction and block subsequent pressor responses in rat lungs. 746 Feb 12

The effects of hydrogen cyanide (HCN) on the neural mechanisms controlling breathing were studied. Two in vitro experimental models were utilized; the brain stem-spinal cord and the medullary slice preparations isolated from neonatal rats. Cyanide, at concentrations deemed lethal in vivo (50 microM), caused a modest (< 15%) depression of the frequency and amplitude of inspiratory rhythmic discharge when added to the bathing media. Moreover, the neuronal network underlying respiratory rhythmogenesis continued to function for hours in the presence of very high concentrations of cyanide (600 microM). We hypothesize that the rapid suppression of breathing caused by cyanide in vivo is due to changes in neuronal excitability in respiratory modulating populations in the CNS rather than due to perturbations of cellular oxidative metabolism or neurons within respiratory rhythm generating centres.
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PMID:Effects of cyanide on the neural mechanisms controlling breathing in the neonatal rat in vitro. 756 81

Tissue oxygen (PO2), K+ (aKe), pH (pHe) and Ca2+ ([Ca2+]e) were measured in the region of the ventral respiratory group (VRG) in the in vitro brainstem-spinal cord preparation of neonatal rats. During tissue anoxia, elicited by superfusion of N2-gassed solutions, an initial increase in the frequency of respiratory activity, lasting between 2 and 12 min, turned into a frequency depression. During anoxia periods of up to 60 min, respiratory activity persisted in solutions containing CO2/bicarbonate, whereas a complete blockade was observed after 15-25 min in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid- (Hepes)-buffered salines. After such anoxic apnea, respiratory rhythmicity could be reactivated by superfusion of hypoxic, CO2/bicarbonate-buffered solutions. In both types of hypoxic solutions, aKe increased by maximally 1.5 mM, whereas an initial increase of pHe by up to 0.05 pH units turned, after 2-4 min, into an acidification which could exceed 0.5 pH units. In contrast, [Ca2+]e remained unaffected by anoxia. Addition of 2-5 mM cyanide (CN-) to oxygenated Hepes-buffered saline evoked an increase in PO2 in the VRG from 100 to more than 300 mmHg. The effects of CN- on respiratory activity, aKe and pHe were almost identical to those during anoxia. In oxygenated, CO2/bicarbonate-free solutions of different pH, however, an increase in pHe in the VRG led to a decrease in respiratory frequency, whereas a fall of pHe produced a frequency acceleration. A rise of aKe in the VRG by more than 2 mM as induced by superfusion of a 7 mM K+ solution led to a sustained increase of respiratory frequency. The results indicate that blockade of aerobic metabolism does not severely perturb K+ and Ca2+ homeostasis and that the biphasic response to anoxia is not directly related to the observed changes in PO2, aKe, pHe, or [Ca2+]e. In the respiratory network of neonatal mammals, CO2 might provide a stimulus for long-term maintenance of respiratory activity under oxygen depletion.
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PMID:Anoxic disturbance of the isolated respiratory network of neonatal rats. 761 41

Unless renal function is impaired or rhabdomyolysis is severe, hyperkalemia is a relatively uncommon metabolic complication of poisoning. In contrast, marked hypokalemia is a more common problem and may have serious sequelae. Most potassium disturbances in acute poisoning are due to disruption of extra-renal control mechanisms, notably the activity of Na+/K+ ATPase and K+ channels. Hypokalemia occurs because of increased Na+/K+ ATPase activity (e.g. beta 2 agonist, theophylline or insulin poisoning), competitive blockade of K+ channels (e.g. barium or chloroquine poisoning), gastrointestinal losses and/or alkalosis. Hyperkalemia follows inhibition of Na+/K+ ATPase activity (e.g. by digoxin), increased uptake of potassium salts, disruption of intermediary metabolism (e.g. cyanide poisoning), activation of K+ channels (e.g. fluoride poisoning), and the presence of acidosis and rhabdomyolysis, particularly if the latter is complicated by renal failure. Hypokalemia results in generalized muscle weakness, paralytic ileus, ECG changes (flat or inverted T waves, prominent U waves, ST segment depression) and cardiac arrhythmias (atrial tachycardia +/- block, AV dissociation, VT, VF). Hyperkalemia is associated with abdominal pain, diarrhea, muscle pain and weakness, ECG changes (tall peaked T waves, ST segment depression, prolonged PR interval, QRS prolongation) and cardiac arrhythmias (VT, VF). Significant disturbances of potassium homeostasis are often unrecognized and may cause considerable morbidity and mortality. Prompt recognition and appropriate treatment of these disturbances could be life-saving.
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PMID:Disturbances of potassium homeostasis in poisoning. 762 96

1. A simple, non-invasive method for distinguishing the central from peripheral effects of respiratory depressant drugs was developed in conscious rats. 2. The procedure involves exposing rats for 5 min to an air mixture containing 8% CO2 (central stimulant) followed by an i.v. bolus injection of 300 micrograms/kg sodium cyanide (peripheral stimulant) and comparing the changes in minute volume and mean inspiratory flow (respiratory drive) before and after drug treatment. 3. The central depressant drugs morphine, xylazine, L-2-phenylisopropyladenosine (L-PIA) and gamma-hydroxybutyric acid. (GHBA) inhibited the CO2-induced increase in minute volume and enhanced the sodium cyanide-induced increase in mean inspiratory flow. 4. Peripheral depression produced by carotid body denervation had no effect on the CO2-induced increase in minute volume and inhibited the sodium cyanide-induced increase in mean inspiratory flow.
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PMID:A non-invasive method for distinguishing central from peripheral nervous system effect of respiratory depressant drugs in conscious rats. 778 30

Glucosinolates, such as sinigrin, and S-methyl cysteine sulphoxide (SMCO), which are found in forage brassica species have been implicated in the low intakes observed among lambs consuming such diets. To test both the individual and interactive effects of these compounds in sheep, all combinations of the sinigrin breakdown products, allyl cyanide (ACN) and allyl isothiocyanate (AITC; 10 mmol/d), and the SMCO metabolite dimethyl disulphide (DMDS; 25 mmol/d) were orally administered twice daily for 5 weeks to forty sheep offered dried grass pellets ad lib. As well as measuring voluntary food intake (VFI), a number of haematological and clinical function tests were conducted to assess the physiological effects of the compounds. VFI was significantly depressed by both ACN and AITC but not by DMDS. DMDS significantly ameliorated the effects of ACN on VFI (P < 0.001). Concentrations of reduced glutathione in the blood were depressed by ACN and AITC and elevated by DMDS but no significant interactions were evident. Elevated plasma gamma-glutamyl transpeptidase (EC 2.3.2.1) activity on ACN and AITC treatments indicated possible liver damage. DMDS elicited a rise in Heinz bodies to 11% by week 2 but this was not reflected in packed cell volume and blood haemoglobin levels which were unaffected by treatment. The increased Heinz body count caused by DMDS was not further influenced by ACN or AITC. In conclusion, the depressive effects of sinigrin breakdown products on VFI were not compounded by the additional presence of DMDS which, on the contrary, lessened the depression of VFI caused by ACN.
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PMID:Effects of oral administration of brassica secondary metabolites, allyl cyanide, allyl isothiocyanate and dimethyl disulphide, on the voluntary food intake and metabolism of sheep. 790 60

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