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

The effects of coformycin, a highly potent and specific inhibitor of the intracellular enzyme adenosine deaminase and the influence of dipyridamole, an inhibitor of the cellular adenosine uptake mechanism, were studied on the adenosine-induced changes in the electrical and mechanical activity of isolated electrically driven left atria of guinea-pig hearts. Adenosine (0.1 mumol/l-1 mmol/l) by itself elicited a concentration-dependent decrease in the action potential duration and contractile force of atrial preparations. Coformycin, when applied in a concentration inducing a nearly complete inhibition of adenosine deaminase activity in intact atrial myocardium (7 mumol/l), enhanced the adenosine-induced reduction both in the duration of the intracellularly recorded action potential and in the contractile force of the atria, preferentially at higher concentrations of adenosine (10 mumol/l-1 mmol/l). The calculated half recovery time during wash-out (t1/2) was found to be about 6 times longer than that of controls (317.5 +/- 47 and 51.3 +/- 4.3 sec, respectively). In contrast with adenosine, the action of 2-chloroadenosine (an adenosine deaminase resistant purine derivative) on the atrial contractile force was not affected in the presence of coformycin. Dipyridamole (0.3 mumol/l) was capable of significantly potentiating the adenosine-induced depression of atrial mechanical activity, mainly at lower concentrations of adenosine (0.1-10 mumol/l). Preincubation of atrial preparations with a combination of coformycin and dipyridamole produced a strong enhancement in the adenosine-induced decrease of mechanical activity at all concentrations of adenosine. It is suggested that adenosine might exert its myocardial actions not only through the known extracellular, but also via possible intracellular purinoceptors.
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PMID:Potentiation of the myocardial actions of adenosine in the presence of coformycin, a specific inhibitor of adenosine deaminase. 710 13

A marked depression of evoked CA1 potentials was observed with the nucleotide analogues a,b-methylene ADP (AOPCP) and adenylimido-diphosphate (AIP) and with 2'-adenosine monophosphate (2'-AMP). While the depression elicited by 5'-nucleotides was completely antagonized by the action of adenosine deaminase, AOPCP and 2'-AMP were only partially antagonized. The findings indicate that nucleotides on their own are capable of modulating synaptic transmission but that the physiologically more prevalent 5'-AMP is mediating its effect via adenosine. By producing this membrane permeable compound and allowing its re-uptake, the 5'-nucleotidase may determine the time course of purinergic action.
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PMID:Effect of adenosine versus adenine nucleotides on evoked potentials in a rat hippocampal slice preparation. 726 30

Adenine dinucleotides such as beta-NAD, alpha-NAD, NADP, 3-aminopyridine adenine dinucleotide, flavin adenine dinucleotide, 3',5'-and 2',5'-adenylyladenosine mimicked the inhibitory effects of adenosine and adenine nucleotides on electrically evoked contractions of the rat and mouse isolated superfused vas deferens. The inhibitory effects were blocked by theophylline or adenosine deaminase, unaffected by the nucleotidase inhibitor alpha, beta-methylene ADP and enhanced by inhibition of adenosine deaminase. The inhibitory effects were associated with a release of purines from the vasa after preloading with [3H]adenosine. It is suggested that these compounds activate a receptor, causing the release of adenosine which is largely responsible for the inhibitions. Diadenosine pyrophosphate and triphosphate caused only depression of the vas twitch, whereas the pentaphosphate and hexaphosphate derivatives caused contraction, followed by inhibition at higher concentrations. These inhibitions were only partly reduced by theophylline or deaminase, but both contractile and inhibitory effects were enhanced by alpha, beta-methylene ADP. Noradrenaline contractions were also reduced by the higher polyphosphates. It is suggested that there may be a receptor for these dinucleotides, located at least in part postjunctionally. The pentaphosphate and hexaphosphate compounds mimicked the effects of nerve stimulation on the guinea-pig bladder, being substantially more potent than beta, gamma-methylene-ATP, and on the taenia caeci, where contraction or relaxation could be produced depending on resting tone.
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PMID:Actions of adenine dinucleotides on the vas deferens, guinea-pig taenia caeci and bladder. 731 4

Field and intracellular potentials were recorded from CA1 pyramidal stratum in submerged slices (at 33 degrees). During "normal" oxygenation (95% O2 + 5% CO2), tonic depression of population spikes and field excitatory postsynaptic potentials by endogenous adenosine was demonstrated by (i) the marked enhancement by the adenosine antagonists 8-(p-sulfophenyl)theophylline (10 microM) and caffeine (0.2 mM), (ii) depression by the transport blocker dipyridamole (5 microM), and (iii) enhancement by exogenous adenosine deaminase (all tested by bath application). Thus, adenosine deaminase (0.5 units/ml) reduced by 10.7 +/- 3.0% (S.E.) the half-maximal stimulus intensity (for population spikes). The effects of adenosine deaminase were prevented by the specific inhibitor, deoxycoformycin (30 microM). In intracellular recordings, excitatory postsynaptic potentials were enhanced in a comparable manner by adenosine deaminase. By contrast, neither deoxycoformycin (5 and 30 microM) nor erythro-9-(2-hydroxy-3-nonyl)adenine (another adenosine deaminase inhibitor; 10 and 50 microM) had significant effects on population spikes. Superfusion with anoxic medium (saturated with 95% N2 + 5% CO2) for 2-3 min suppressed population spikes reversibly, by a mechanism involving adenosine, because 8-(p-sulfophenyl)theophylline (10 microM) and caffeine (0.2 mM) delayed the onset of anoxic block and accelerated the subsequent recovery, and the recovery was much slower or incomplete in the presence of dipyramidole (0.5 microM). However, the anoxic suppression of population spikes was not affected by deoxycoformycin (30 microM) or erythro-9-(2-hydroxy-3-nonyl)adenine (10 microM); the corresponding 50% postanoxic recovery times were also unchanged (e.g. 4.0 +/- 0.2 min for controls and 4.1 +/- 0.3 min in deoxycoformycin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous adenosine deaminase does not modulate synaptic transmission in rat hippocampal slices under normoxic or hypoxic conditions. 789 60

Serum adenosine deaminase (ADA) of 74 liver cirrhosis patients and 100 healthy subjects as control were examined with improved Martinek microassay and peripheral T lymphocyte subsets of 38 liver cirrhosis patients and 60 healthy subjects studied by indirect immunofluorescence assay (IFA) for exploring the relationship between them and syndrome types of TCM. The result showed that level of ADA of liver cirrhosis patients was higher than that of control (P < 0.01) and increased in following order: the type of Liver-energy Depression and Spleen Deficiency, that of Heat-Stagnation and Blood Stasis and that of Yin-Deficiency and Microvessel Obstruction. The difference of serum ADA among the types were significant (P < 0.01). The result also showed that OKT8 of liver cirrhosis patients was higher, the ratio of OKT4/OKT8 was lower than the healthy subjects (P < 0.05-0.01), but the difference among the types were not significant (P > 0.05). Serum ADA seemed to be one of the reference indexes in differentiating syndrome types of TCM, determining the patient's condition and prognosis.
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PMID:[Correlation between serum adenosine deaminase, peripheral T lymphocyte subsets and syndrome types of traditional Chinese medicine in liver-cirrhosis patients]. 795 Jan 82

Predialysis erythrocyte adenosine deaminase activity was depressed in 12 of 20 patients receiving hemodialysis. In contrast, in 17 patients a marked rise in enzyme activity was observed subsequent to dialysis. Six patients had evidence of neuropathy. Predialysis plasma inhibited normal enzyme activity by an average of 36%, but postdialysis plasma had minimal inhibitory effect. A low molecular weight substance or substances, isolated from the dialysate of uremics, inhibited adenosine deaminase activity by 38%. Three patients having the longest courses of dialysis had no neuropathy and showed no depression of activity, with their plasma failing to inhibit normal activity. It is suggested that accumulation of low molecular weight toxins that depress adenosine deaminase activity may lead to myelin sheath degeneration with subsequent neuropathy. By removing the inhibitor, dialysis may permit nerve repair and eventual recovery.
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PMID:Uremic toxins and adenosine deaminase activity. 800 Dec 88

1. Previous work has suggested that presynaptic effects of adenosine may be dependent on divalent cations. The present study was undertaken to determine whether a similar requirement existed at postsynaptic sites. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum or antidromic stimulation of the alveus. In antidromic stimulation experiments, CaCl2 was omitted (calcium-free medium) or reduced to 0.24 mM (low calcium medium) and in some experiments MgSO4 was increased to 2 mM. Kynurenic acid at concentrations of 1 and 5 mM in calcium-free medium and 1 mM in low calcium medium had no effect on secondary spike size. 3. Adenosine and baclofen induced a concentration-dependent reduction in the amplitude of orthodromic potentials with maximum effects at 20 and 5 microM respectively. 4. In nominally calcium-free medium, bursts of multiple population spikes were obtained in response to antidromic stimulation. Adenosine had little effect in reducing the secondary spike amplitude. At high concentration (2 mM) an initial depression was seen which declined within 3-5 min. 5. Sensitivity to adenosine was restored in low calcium medium or by raising magnesium. Although raising the divalent cation concentration increased the inhibitory effect of adenosine, desensitization was still seen. 6. 2-Chloroadenosine (100-500 microM) and R-PIA (50 microM), which are not substrates for either the nucleoside transporters or adenosine deaminase, were inactive in the absence of calcium. S-(2-hydroxy-5 nitrobenzyl)-6-thioinosine, an adenosine uptake blocker, at a concentration 100 MicroM had no effect on secondary potential size and did not restore adenosine sensitivity in calcium-free medium.7. Thapsigargin, which discharges intracellular calcium stores, had no significant effect at 1 MicroM on the bursts of action potentials and did not change the effect of 0.5 mM adenosine in calcium-free medium.8. Unlike adenosine, baclofen concentration-dependently reduced the secondary spike size in calcium free medium and no sign of recovery was observed during maintained superfusion for up to 45 min. No cross-desensitization was seen between baclofen and adenosine.9. Applications of adenosine locally by pressure to neuronal somata or dendrites still resulted in desensitized responses in calcium-free medium.10. It is concluded that the postsynaptic sensitivity to adenosine is dependent on the concentration of divalent cations in the extracellular space implying an effect of cations on adenosine receptor activation or transduction processes.
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PMID:The effect of calcium removal on the suppression by adenosine of epileptiform activity in the hippocampus: demonstration of desensitization. 803 57

1. The hypothesis that ATP released by presynaptic stimulation is hydrolysed to adenosine and mediates prejunctional neuromuscular depression was tested at vertebrate neuromuscular junctions. Electrophysiological recordings of evoked acetylcholine (ACh) release and perineural ionic currents at motor nerve endings were made using the frog cutaneous pectoris nerve-muscle preparation. Either tubocurarine or alpha-bungarotoxin was used to block muscle contractions. 2. Either alpha,beta-methylene ADP (which inhibits ecto-5'nucleotidases and thus prevents the degradation of ATP to adenosine) or selective adenosine receptor antagonists (8-cyclo-pentyl alkyl xanthines) prevented the inhibitory effects of exogenous ATP on ACh release in response to low-frequency nerve stimulation. These results confirm earlier findings that ATP must be hydrolysed to adenosine to inhibit ACh release. 3. The presence of alpha,beta-methylene ADP completely prevented neuromuscular depression in response to repetitive high-frequency nerve stimulation (0.5-1 Hz). alpha,beta-Methylene ADP had no effect on ACh secretion under conditions where ACh release is well maintained (low-frequency stimulation, 0.05 Hz). 4. Selective adenosine receptor antagonists completely eliminated neuromuscular depression produced by repetitive high-frequency nerve stimulation (1.0 Hz) but had no effect on ACh release at low frequencies of stimulation (0.05 Hz). 5. Exogenous adenosine deaminase (5 i.u. ml-1), which degrades adenosine to its inactive nucleoside inosine, also eliminated neuromuscular depression but had no significant effect on ACh release at frequencies of nerve stimulation too low to produce prejunctional depression. 6. During maximal neuromuscular depression, the effects of exogenous adenosine or 2-chloroadenosine, an adenosine agonist, were occluded. 7. The calcium-sensitive component of perineurial recordings of motor nerve terminal currents did not change during depression or during application of adenosine receptor antagonists and adenosine deaminase, suggesting that neuromuscular depression in this species was not associated with changes in presynaptic Ca2+ currents. 8. These results suggest that, under the conditions of these experiments, endogenous ATP, after hydrolysis to adenosine, causes prejunctional neuromuscular depression. This inhibitory effect of endogenous adenosine occurs at a site distal to the locus of Ca2+ entry in the frog.
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PMID:ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings. 807 78

1. Using an extracellular recording technique, we have investigated the site of action of adenosine and muscarine on the rat superior cervical ganglion (SCG). The adenosine-induced hyperpolarization and muscarine-induced depolarization of ganglia were localized to the cell bodies of the ganglia. Responses to muscarine and adenosine were larger when recorded via the internal carotid nerve (ICN) compared with the external carotid nerve. Depression of the response to muscarine by adenosine was similar for both nerve trunks. 2. The effects of adenosine and cyclic nucleotides on the d.c. potential and the depolarization to muscarine were examined by recording via the ICN. Adenosine at concentrations up to 1 mM produced concentration-dependent hyperpolarizations. Hyperpolarization induced by 100 microM adenosine was unaffected by 1 microM tetrodotoxin or the muscarinic M1-receptor antagonist pirenzepine (0.3 microM). In contrast, hyperpolarizations to 100 microM adenosine were significantly reduced by 10 microM 8-phenytheophylline (55 +/- 7 microV vs 15 +/- 9 microV, P < 0.01, n = 4). Two agents known to increase intracellular cAMP, i.e. 8-bromo-cyclic-adenosine-3'-5' monophosphate (8BrcAMP) and isoprenaline, depolarized ganglia. Depolarizations to 100 nM mucarine were significantly depressed by adenosine (100 microM) by 26 +/- 2% (n = 61), but unaltered by 8BrcAMP or cyclic guanosine-3'-5' monophosphate. 3. Dipyridamole and hydroxy-nitro-benzylthioguanosine (inhibitors of adenosine transport) and erythro-6-amino-9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibitor of adenosine deaminase), potentiated the depression by adenosine of the response to muscarine, and the hyperpolarization to adenosine respectively. However, there was no evidence to support the hypothesis that there was spontaneous release of endogenous adenosine under the conditions of study, as dipyridamole or EHNA did not alter the control d.c. potential or the depolarization to muscarine. 4. It is concluded that the ability of adenosine to hyperpolarize and depress the response of the rat SCG to muscarine is due to the direct activation of postsynaptic somatodendritic P1-purinoceptors and unlikely to be mediated by an increase in intracellular cAMP. In addition the rat SCG has mechanisms for both the uptake and inactivation of adenosine.
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PMID:On the site of action and inactivation of adenosine by the rat superior cervical ganglion. 851 24

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


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