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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine is an endogenous cardioprotective substance. The present study examines whether exogenous adenosine attenuates cardiac injury induced by oxidative stress. Rat hearts (Langendorff model) were perfused with H2O2 (180 microM) for 10 min, then recovered for 60 min (n = 10). In other groups adenosine 55 microM, 11 0 microM, or 220 microM (n = 10 in each) was given in addition to H2O2 throughout perfusion. Control perfusion with Krebs Henseleit only (n = 7), adenosine 110 microM throughout perfusion (n = 7), and adenosine 110 microM as an intervention (n = 7) was performed. The hearts were paced at 320 beats/min. Left ventricular systolic (LVSP) and end-diastolic (LVEDP) pressures were measured together with coronary flow (CF), and left ventricular developed pressure (LVDP = LVSP - LVEDP) was calculated. H2O2 decreased LVSP from 105 +/- 8 to 60 +/- 5 mmHg (mean +/- SEM) after 10 min infusion (p < 0.008). Adenosine did not attenuate the decrease of LVSP. LVEDP increased from 0 to 59 +/- 10 mmHg (p < 0.004) and 62 +/- 11 mmHg 5 and 15 min after end of infusion of H2O2, respectively. Neither 55 microM nor 220 microM adenosine inhibited the H2O2-induced increase of LVEDP. Adenosine 110 microM attenuated the increase after 15 (15 +/- 4 mmHg, p < 0.004) and 25 min observation (26 +/- 7 mmHg, p < 0.012). Adenosine did not attenuate the reduction of LVDP. CF initially increased during infusion of H2O2, thereafter decreased. Hearts given adenosine had higher basal CF, and CF did not increase after H2O2. Control perfusion with adenosine, given throughout perfusion or as an intervention, increased CF and tended to increase LVSP. In summary, adenosine did not inhibit H2O2-induced depression of contractility or reduction of CF. One concentration of adenosine (110 microM) attenuated H2O2-induced impairment of relaxation. Exogenous adenosine does not have an important influence on functional injury caused by exogenous oxidants.
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PMID:The effect of exogenous adenosine on functional injury caused by hydrogen peroxide in the isolated rat heart. 874 90

Adenosine versus Verapamil and other Antiarrhythmic Drugs: Paroxysmal supraventricular tachycardia is the most common sustained arrhythmia during pregnancy. Verapamil has been the most commonly used agent for the treatment of PSVT with a narrow QRS complex. Potential side effects of verapamil including systemic hypotension, acute heart failure, bradyarrhythmia and heart block may occur in pregnant women; after placental transfer bradycardia, heart block, depression of contractility and hypotension may be induced in the fetus. We report on the case of a 22-year old pregnant woman with hypotension and tachycardia, who was admitted for suspected haemorhagic shock. Indeed, she suffered from paroxysmal supraventricular tachycardia, which was successfully terminated by intravenous adenosine. Because of its known rapid onset, high effectivity, low incidence and brevity of side effects in the mother and comparative safety in the fetus, adenosine seems to be the drug of choice for treating PSVT during pregnancy.
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PMID:[Paroxysmal supraventricular tachycardia in pregnancy. Value of adenosine and other anti-arrhythmia agents]. 876 89

Adenosine is a potent neuromodulator in the CNS, but the mechanisms that regulate adenosine concentrations in the extracellular space remain unclear. The present study demonstrates that increasing the intracellular concentration of adenosine in a single hippocampal CA1 pyramidal neuron selectively inhibits the excitatory postsynaptic potentials in that cell. Loading neurons with high concentrations of adenosine via the whole-cell patch-clamp technique did not affect the GABAA-mediated inhibitory postsynaptic potentials, the membrane resistance, or the holding current, whereas it significantly increased the adenosine receptor-mediated depression of excitatory postsynaptic currents. The effects of adenosine could not be mimicked by an agonist at the intracellular adenosine P-site, but the effects could be antagonized by a charged adenosine receptor antagonist and by adenosine deaminase, demonstrating that the effect was mediated via adenosine acting at extracellular adenosine receptors. The effect of adenosine loading was not blocked by BaCl2 and therefore was not caused by an adenosine-activated postsynaptic potassium conductance. Adenosine loading increased the paired-pulse facilitation ratio, demonstrating that the effect was mediated by presynaptic adenosine receptors. Finally, simultaneous extracellular field recordings demonstrated that the increase in extracellular adenosine was confined to excitatory synaptic inputs to the loaded cell. These data demonstrate that elevating the intracellular concentration of adenosine in a single CA1 pyramidal neuron induces the release of adenosine into the extracellular space in such a way that it selectively inhibits the excitatory inputs to that cell, and the data support the general conclusion that adenosine is a retrograde messenger used by pyramidal neurons to regulate their excitatory input.
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PMID:Modulation of excitatory synaptic transmission by adenosine released from single hippocampal pyramidal neurons. 879 16

The measurement of cerebral extracellular lactate levels has been suggested to be used to monitor cerebral function in intensive care However, although an increase of extracellular lactate levels is a sensitive parameter for increased cellular activity in general, it will be shown that its prognostic value is limited in regard to the severity of the impairment of cellular function. As an alternative the measurement of the extracellular levels of inorganic phosphate (IP) or adenosine is proposed here: Whereas extracellular lactate levels increased rapidly to about the same extents during ischemia (IS) and spreading depression (SD), IP rose during IS only. Adenosine, on the other hand, increased during both events to a different degree. If, therefore, lactate was the only parameter to be monitored after a cerebral insult, the results would not allow to discriminate between a transient, spontaneously recovering event as a SD and a long lasting or an irreversible loss of cell function as in persisting ischemia/hypoxia. The measurement of IP, therefore, seems to be more suitable than that of lactate or adenosine since IP will appear within the extracellular space only after a sustained failure of membrane function. Thus, the measurement of IP changes turned out to be the more useful parameter for intensive care supervision.
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PMID:The measurement of extracellular inorganic phosphate gives a more reliable indication for severe impairment of cerebral cell function and cell death than the measurement of extracellular lactate. 887 Jul 97

Adenosine is considered an important neuromodulator of the nervous system acting at pre-, post- and non-synaptic levels. In the present review we describe how adenosine modifies paired-pulse facilitation (PPF), posttetanic depression (PTD), long-term potentiation (LTP), long-term depression (LTD) and depotentiation at the hippocampus, and therefore how this nucleoside modulates synaptic plasticity.
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PMID:Adenosine and neuronal plasticity. 901 Apr 79

Involvement of neurotransmitters in metabolic depression under hypoxia and hypercapnia was examined in Sipunculus nudus. Concentration changes of several putative neurotransmitters in nervous tissue during anoxic or hypercapnic exposure or during combined anoxia and hypercapnia were determined. Among amino acids (gamma-aminobutyric acid, glutamate, glycine, taurine, serine, and aspartate) and monoamines (serotonin, dopamine, and norepinephrine), some changes were significant, but none were consistent with metabolic depression under all experimental conditions applied. Only the neuromodulator adenosine displayed concentration changes in accordance with metabolic depression under all experimental conditions. Levels increased during anoxia, during hypercapnia, and to an even greater extent during anoxic hypercapnia. Adenosine infusions into coelomic fluid via an indwelling catheter induced a significant depression of the normocapnic rate of O2 consumption from 0.36 +/- 0.04 to a minimum of 0.24 +/- 0.02 (SE) mumol.g-1.h-1 after 90 min (n = 6). Application of the adenosine antagonist theophylline caused a transient rise in O2 consumption 30 min after infusion during hypercapnia but not during normocapnia. Effects of adenosine and theophylline were observed in intact individuals but not in isolated body wall musculature. The results provide evidence for a role of adenosine in inducing metabolic depression in S. nudus, probably through the established effects of decreasing neuronal excitability and neurotransmitter release. In consideration of our previous finding that metabolic depression in isolated body wall musculature was elicited by extracellular acidosis, it is concluded that central and cellular mechanisms combine to contribute to the overall reduction in metabolic rate in S. nudus.
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PMID:A role for adenosine in metabolic depression in the marine invertebrate Sipunculus nudus. 903 28

The rapid suppression of CNS function produced by cyanide (CN) was studied by field, intracellular, and whole-cell recording in hippocampal slices (at 33-34 degrees C). Population spikes and field EPSPs were depressed by 4-5 min bath applications of 50-100 microM CN (IC50 was 18 miroM for spikes and 72 microM for EPSPs). The actions of CN were reversibly suppressed by the adenosine antagonists 8-sulfophenyltheophylline (8-SPT; 10 microM) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.2 microM), potentiated by the adenosine transport inhibitor dipyridamole (0.5 microM), but unaffected by the KATP channel blocker glyburide (10 microM). Therefore the CN-induced reductions of synaptic efficacy and postsynaptic excitability-demonstrated by synaptic input:output plots-are mediated mainly by adenosine. In whole-cell or intracellular recordings, CN depressed EPSCs and elicited an increase in input conductance and an outward current, the reversal potential of which was approximately -90 mV (indicating that K+ was the major carrier). These effects also were attenuated by 8-SPT. In the presence of 1 mM Ba, CN had no significant postsynaptic action; Cs (2 mM) also prevented CN-induced outward currents but only partly blocked the increase in conductance. Another 8-SPT-sensitive action of CN was to depress hyperpolarization-activated slow inward relaxations (Q current). At room temperature (22-24 degrees C), although it did not change holding current and slow inward relaxations, CN raised the input conductance; this effect also was prevented by 8-SPT (10 microM), but not by glyburide (10 microM). Adenosine release thus appears to be the major link between acute CN poisoning and early depression of CNS synaptic function.
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PMID:Adenosine release mediates cyanide-induced suppression of CA1 neuronal activity. 906 96

Energy deprivation, as a result of aglycemia, leads to depression of the central synaptic transmission. Endogenous adenosine has been implicated in this depressant effect. We have studied the possible involvement of endogenous adenosine in the depression of corticostriatal excitatory transmission induced by glucose deprivation by using intracellular recordings in brain slices. After stimulation of corticostriatal fibers, EPSPs were recorded from striatal spiny neurons. Adenosine (3-300 microM) or brief periods (5-10 min) of aglycemia reduced the EPSP amplitude but did not alter the membrane potential and the resistance of the recorded cells. These inhibitory effects were not associated with an alteration of the postsynaptic sensitivity to exogenous glutamate but were coupled with an increased paired-pulse facilitation, suggesting the involvement of presynaptic mechanisms. A delayed postsynaptic membrane depolarization/inward current was detected after 15-20 min of glucose deprivation. The presynaptic inhibitory effects induced by adenosine and aglycemia were both antagonized either by the nonselective adenosine receptor antagonist caffeine (2.5 mM) or by the A1 receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine (CPT, 1 microM) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300 nM). Conversely, these antagonists affected neither the delayed membrane depolarization/inward current nor the underlying conductance increase produced by glucose deprivation. The ATP-sensitive potassium channel blockers tolbutamide (1 mM) and glipizide (100 nM) had no effect on the aglycemia-induced decrease of EPSP amplitude. Our data demonstrate that endogenous adenosine acting on A1 receptors mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses, whereas ATP-dependent potassium channels do not play a significant role in this presynaptic inhibition.
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PMID:Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses. 916 11

1. The modulation by adenosine of GABA-activated current (IGADA) was studied in freshly isolated rat dorsal root ganglion (DRG) neurons using the whole-cell patch-clamp technique. 2. In most of the DRG neurons examined (68/90, 75.5%) adenosine (1-10 microM) suppressed IGABA, while in some neurons examined, it potentiated (16/90, 17.8%) IGABA. It exerted no effects on IGABA in a few cells (6/90, 6.7%). 3. Adenosine shifted the GABA concentration-response curve downward with no significant change of the EC50. The maximal response to GABA was suppressed by 29.6 +/- 2.6%. The adenosine-induced inhibition of IGABA showed no voltage dependence. 4. 8-Cyclopentyl-1,3-dimethylxanthine (DPCPX; 1 microM), a selective A1 adenosine receptor antagonist, partially reversed adenosine inhibition of IGABA and completely blocked N6-cyclo-hexyladenosine (CHA; an A1 adenosine receptor agonist) inhibition of IGABA. DPCPX (1 microM) also blocked the suppression of IGABA by 2-chloroadenosine (CADO). CGS21680, a selective A2A adenosine receptor agonist, did not inhibit IGABA and DMPX, a selective A2A adenosine receptor antagonist, did not prevent adenosine inhibition of IGABA. 5. Intracellular application of H-7 (20 microM; a protein kinase C inhibitor) reversed adenosine inhibition of IGABA while inclusion of cAMP (1 mM), H-9 (20 microM; a protein kinase A inhibitor) and BAPTA (10 mM; a chelator of calcium ions) in the recording pipette did not affect the depression of IGABA by adenosine. IGABA was also suppressed by internal perfusion of PMA, a protein kinase C activator. 6. The results suggest that adenosine, as a neuromodulator, exerts a modulatory effect on the GABA-induced presynaptic inhibition in primary sensory transmission.
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PMID:Modulation by adenosine of GABA-activated current in rat dorsal root ganglion neurons. 917 95

The increased tolerance to myocardial ischemia observed during the second of two sequential exercise tests, i.e. the warm-up phenomenon, has been proposed as a clinical model of ischemic preconditioning. Adenosine appears to be a mediator of ischemic preconditioning in both experimental and clinical settings. The purpose of this study was to investigate the role of A1 adenosine receptors in the warm-up phenomenon. A double-blind, placebo-controlled, cross-over design was used. Twelve patients with coronary artery disease and positive exercise test were randomized to receive either bamiphylline, a selective A1 adenosine receptor antagonist, or placebo, immediately prior to two consecutive treadmill exercise tests carried out on day 1. Then, on day 2 all patients underwent two consecutive exercise tests immediately after administration of the remaining treatment. During the first exercise test, bamiphylline, compared to placebo, increased the time to and rate-pressure product at 1.5 mm ST-segment depression (from 317 +/- 118 to 423 +/- 127 s, p < 0.05 and from 199 +/- 38 to 230 +/- 36 b/min.mmHg.10(2), p < 0.05, respectively). After both placebo and bamiphylline infusions, time to 1.5 mm ST-segment depression during the second exercise test was greater than that during the first test (445 +/- 121 vs 317 +/- 118 s, p < 0.001 and 483 +/- 128 vs 423 +/- 127 s, p < 0.05, respectively), as was rate-pressure product at 1.5 mm ST-segment depression (228 +/- 40 vs 199 +/- 38 b/min.mmHg.10(2), p < 0.01 and 253 +/- 42 vs 230 +/- 36 b/min.mmHg.10(2), p < 0.05, respectively). In conclusion, bamiphylline, at a dose able to increase ischemic threshold and exercise tolerance compared to placebo, does not prevent the warm-up phenomenon. These findings suggest that, in the setting of the warm-up phenomenon, A1 adenosine receptor blockade is insufficient to prevent ischemic preconditioning.
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PMID:Effects of A1 adenosine receptor blockade on the warm-up phenomenon. 918 7


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