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)

The effects of adenosine on inhibitory synaptic transmission in area CA1 were examined using the rat hippocampal slice preparation and intracellular recording. Adenosine did not change fast inhibitory synaptic potentials (IPSPs) but depressed late IPSPs evoked by direct activation of interneurons in the presence of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Directly activated IPSPs were unchanged by the selective adenosine A1 receptor antagonist 8-cyclopentyltheophylline (CPT), but CPT reversed hyperpolarization and depression of late IPSPs produced by adenosine. These results indicate that adenosine depresses disynaptic IPSPs in area CA1 by decreasing synaptic activation of inhibitory neurons.
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PMID:Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus. 167 45

The effects of 5-amino-4-imidazolecarboxamide riboside (rAICA) on coronary adenosine efflux were examined in blood-free perfused working rat heart preparations subjected to mild (70% O2) and severe hypoxia (45% O2). Under these hypoxic conditions, no significant increase of coronary adenosine effluxes was observed in the presence of 300 microM rAICA alone. However, rAICA-induced augmentation of coronary adenosine efflux during hypoxia was revealed in the presence of an adenosine deaminase inhibitor, erythro-(2-hydroxy-3-nonyl)adenine hydrochloride, indicating that the failure to note the increase in coronary adenosine efflux was due to a rapid deamination of adenosine to inosine. A depression in heart rate during mild and severe hypoxia was significantly exacerbated by rAICA. These effects on heart rate were mediated by adenosine, since they were effectively blocked by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine, a selective adenosine A1-receptor antagonist. These results suggest that rAICA elevates adenosine efflux during hypoxia.
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PMID:5-Amino-4-imidazolecarboxamide riboside raises adenosine in perfused hypoxic rat heart. 180 58

Exposure of rat hippocampal slices to hypoxic conditions for 15 min produced a rapid, profound, but completely reversible depression of evoked synaptic potentials. The specific A1 adenosine receptor antagonist 8-cyclopentyltheophylline (8-CPT) significantly reduced hypoxia-induced synaptic depression in a concentration-dependent manner. It is concluded that adenosine, which is neuroprotective when exogenously applied during severe hypoxia because of its ability to depress synaptic transmission, may have an important and exploitable endogenous role in the protection of sensitive neurons.
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PMID:The adenosine antagonist 8-cyclopentyltheophylline reduces the depression of hippocampal neuronal responses during hypoxia. 235 68

Correlative studies examining: (1) the binding of [3H]cyclohexyladenosine to A1 adenosine receptor sites, and (2) the depressive action of adenosine on evoked activity, were performed in the hippocampal formation. A greater number of A1 sites was observed in the dorsal versus ventral aspect of the hippocampus, and a larger depression of evoked potentials by adenosine was obtained in the dorsal aspect. These observations suggest that a differential density of A1 receptors might control the magnitude of modulatory action by adenosine on hippocampal circuitry.
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PMID:Regulation of the strength of adenosine modulation in the hippocampus by a differential distribution of the density of A1 receptors. 629 83

1. The modulatory effects of intracellularly injected adenosine on membrane potential, input resistance and spontaneous or evoked synaptic activity were determined in respiratory neurones of the ventral respiratory group. 2. The membrane potential hyperpolarized and sometimes reached values which were beyond the equilibrium potential of Cl(-)-dependent IPSPs. At the same time, neuronal input resistance decreased. 3. Spontaneous and stimulus-evoked postsynaptic activities were decreased, as were mean respiratory drive potentials. 4. Systemic injection of the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.01-0.05 mg kg-1) resulted in an increase in mean peak phrenic nerve activity when arterial chemoreceptors were denervated. In contrast, phrenic nerve activity decreased when arterial chemoreceptors were left intact. 5. The depressant effect of adenosine on synaptic activity was abolished after systemic DPCPX administration. DPCPX caused an increase in respiratory drive potentials, increased the amplitude of stimulus-evoked IPSPs, and hyperpolarized membrane potential. 6. Administration of DPCPX blocked the early hypoxic depression of stimulus-evoked IPSPs, doubled the delay of onset of hypoxic apnoea and shortened the time necessary for recovery of the respiratory rhythm. 7. The data indicate that adenosine acts on pre- and postsynaptic A1 receptors resulting in postsynaptic membrane hyperpolarization and depression of synaptic transmission. Blockade of A1 receptors increases respiratory activity, indicating that adenosine A1 receptors are tonically activated under control conditions. Further activation contributes to the hypoxic depression of synaptic transmission in the respiratory network.
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PMID:Adenosinergic modulation of respiratory neurones and hypoxic responses in the anaesthetized cat. 777 57

Spreading depression (SD) is known to be involved in the N-methyl-D-aspartate receptor-mediated neuronal damage. In urethane-anesthetized rats, we examined the release of adenosine and glutamate during SD induced by microdialysis of high K+ perfusate through the hippocampal CA1 area. The effects of endogenous adenosine upon SD were studied by applying an adenosine antagonist, theophylline (1 mM) and by a simultaneous application of adenosine uptake blockers, dipyridamole (DPR) (100 microM) and nitrobenzylthioinosine (NBI) (50 microM). The dialysates were sampled every 5 or 10 min and analyzed by HPLC. SD was identified by flattening of background EEg and disappearance of population spikes recorded from the pyramidal cell layer of CA1 area by a glass microelectrode. Adenosine and glutamate release was enhanced significantly in association with the occurrence of SD. Theophylline increased the release of glutamate and the incidence of SD and decreased the latency of the SD occurrence. DPR+NBI decreased the release of glutamate and the occurrence of SD, but increased extracellular adenosine concentration. The effects of DPR+NBI were blocked by application of a selective antagonist of adenosine A1 receptor, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.1 microM). These findings suggest that endogenous adenosine exerts inhibitory influences upon the development of SD and the glutamate release through the A1 receptor in rat hippocampus.
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PMID:Endogenous adenosine exerts inhibitory effects upon the development of spreading depression and glutamate release induced by microdialysis with high K+ in rat hippocampus. 783 53

Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the N-methyl-D-aspartate (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 +/- 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 +/- 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 +/- 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 +/- 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 +/- 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8- cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus. 783 77

Adenosine is present in the mammalian brain in large amounts and has potent effects on neuronal activity, but its role in neural signaling is poorly understood. The glutamate receptor agonist N-methyl-D-aspartate (NMDA) caused a presynaptic depression of excitatory synaptic transmission in the CA1 region of guinea pig hippocampal slices. This depression was blocked by an adenosine A1 receptor antagonist, which suggests that activation of the NMDA subtype of glutamate receptor raises the concentration of extracellular adenosine, which acts on presynaptic inhibitory A1 receptors. Strong tetanic stimulation caused a heterosynaptic inhibition that was blocked by both NMDA and A1 receptor antagonists. Enkephalin, which selectively inhibits interneurons, antagonized the heterosynaptic inhibition. These findings suggest that synaptically released glutamate activates NMDA receptors, which in turn releases adenosine, at least in part from interneurons, that acts at a distance to inhibit presynaptically the release of glutamate from excitatory synapses. Thus, interneurons may mediate a widespread purinergic presynaptic inhibition.
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PMID:Release of adenosine by activation of NMDA receptors in the hippocampus. 791 85

The neuromodulator adenosine is known to decrease neurotransmitter release at the neuromuscular junction by activation of an A1 adenosine receptor coupled to a pertussis toxin-sensitive G protein. Among the mechanisms that could contribute to the depression of neurotransmitter release is reduced entry of calcium through channels located in the presynaptic terminal. In the present study, we have examined the effects of adenosine on high-voltage-activated (HVA) calcium currents in motoneurons, the presynaptic cells of the neuromuscular junction. The motoneurons were isolated from embryonic mice, placed in primary tissue culture for 16 hr, and analyzed by means of the whole-cell patch-clamp technique. Adenosine (40 microM) reduced both transient and sustained components of HVA calcium current. This effect was blocked by the A1 antagonist 8-cyclopentyltheophylline (CPT; 100 nM) and was mimicked by the A1 agonist N6-cyclohexyladenosine (CHA; 50 nM to 10 microM) but not by the A2a agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine (CGS-21680; 1 micron). Pretreatment with pertussis toxin (200 ng/ml, > 16 hr) abolished the depression of HVA calcium current by adenosine receptor activation. Brief (3 min) exposure of the cells to 10 microM omega-conotoxin GVIA irreversibly blocked a part of the HVA current, which can therefore be attributed to N-type channels; the remaining current was unaffected by adenosine receptor activation. Hence, it appears that adenosine decreases only the N-current portion of HVA current and that this inhibition occurs via an A1 receptor linked to a pertussis toxin-sensitive G protein. Other investigators have shown that N-type channels do not play a primary role in eliciting transmitter release at the mammalian neuromuscular junction. Thus, it is uncertain what motoneuronal functions are influenced by adenosine modulation of N-type channels.
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PMID:Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons. 820 77

The effect of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1 adenosine receptor antagonist, was studied at frog motor nerve endings in the hope of determining whether the inhibitory effects of exogenous or endogenous adenosine on neurotransmitter release are mediated by an A1 receptor or the postulated prejunctional "A3 receptor." These putative A3 receptors have been reported to have a lower affinity for DPCPX (>> 1 nM) than A1 receptors (50-190 pM) and have been linked to changes in Ca2+ translocation. The affinity of DPCPX as an antagonist of exogenous adenosine at frog motor nerve endings was calculated by using the Schild equation and found to range from 25 to 200 pM (n = 12). These values are consistent with the presence of A1 receptors. The effect of endogenous adenosine as a mediator of prejunctional neuromuscular depression produced by repetitive nerve impulses was fully reversed by 100 pM DPCPX. Neither prejunctional neuromuscular depression produced by endogenous or exogenous adenosine nor the reversal of depression by DPCPX was associated with changes in nerve terminal Ca2+ currents. The results demonstrate that endogenous or exogenous adenosine mediates neuromuscular depression in the frog, via an A1 receptor.
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PMID:A selective adenosine antagonist (8-cyclopentyl-1,3-dipropylxanthine) eliminates both neuromuscular depression and the action of exogenous adenosine by an effect on A1 receptors. 823 34


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