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

1. The effects of dibutyryl guanosine 3',5'-cyclic monophosphate (db-cyclic GMP) were studied in vitro on calcium channels of neurones in rabbit vesical parasympathetic ganglia, using intracellular and single-electrode voltage-clamp recordings. 2. Db-cyclic GMP (100 microM) caused membrane depolarization associated with a decrease in membrane input resistance and an after-hyperpolarization associated with an increase in membrane input resistance. 3. Db-cyclic GMP (0.01-1 mM) caused a concentration-dependent, transient inward current followed by a long-lasting outward current. Membrane conductance was increased and decreased during the inward and outward currents, respectively. 4. The db-cyclic GMP-induced inward current was depressed in nominally calcium-free solutions, by cobalt (1 mM) and nicardipine (10 microM). The mean reversal potentials of the inward current were +42 and -20 mV in the presence and absence of calcium in the external solution, respectively. 5. The db-cyclic GMP-induced inward current was not altered by lowering the external sodium concentration, raising external potassium concentration or by intracellular injection of caesium. 6. A calcium-insensitive component of the db-cyclic GMP-induced current was increased by lowering the external chloride concentration and blocked by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid, a chloride channel blocker. 7. Voltage-dependent, high-threshold calcium currents were depressed during the db-cyclic GMP-induced inward current and facilitated during the outward current. 8. Cyclic GMP was less potent than db-cyclic GMP in causing both inward and outward currents or modulation of calcium currents. GTP, GDP, GMP, guanosine, 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin did not alter the holding current or voltage-dependent calcium currents. 9. It is concluded that intracellular cyclic GMP causes not only activation of resting calcium and chloride channels but also a transient depression followed by long-lasting facilitation of voltage-dependent calcium currents in neurones of vesical parasympathetic ganglia.
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PMID:Guanosine 3',5'-cyclic monophosphate regulates calcium channels in neurones of rabbit vesical pelvic ganglia. 133 64

1. The effects of endothelin were studied, in vitro, on neurones contained in the rabbit vesical pelvic ganglion by use of intracellular and single-electrode voltage clamp techniques under conditions where sodium and potassium channels were blocked. 2. In the current-clamp experiments, endothelin (1 microM) caused a depolarization followed by a hyperpolarization of the membrane potential. In the voltage-clamp experiments, endothelin (0.01-1 microM) caused an inward current followed by an outward current in a concentration-dependent manner. 3. Membrane conductance was increased during the endothelin-induced depolarization and inward current. Membrane conductance was decreased during the endothelin-induced hyperpolarization and outward current. 4. The endothelin-induced inward and outward currents were not altered by lowering external sodium concentration or raising external potassium concentration. 5. The endothelin-induced inward current was depressed (mean 72%) in a Krebs solution containing nominally zero calcium and high magnesium. These results suggest that a predominent component of the endothelin-induced inward current is mediated by calcium ions. 6. The calcium-insensitive component of the inward current was abolished by a chloride channel blocker, 4-acetamide-4'-isothiocyanostilbene-2,2'-disulphonic acid. The mean reversal potential for the calcium-insensitive component of the inward current was -18 mV. This value is near the equilibrium potential for chloride. Thus, it is presumed that the calcium-insensitive component of the inward current is carried by chloride ions. 7. Endothelin caused an initial depression followed by a long lasting facilitation of both rapidly and slowly decaying components of high-threshold calcium channel currents (N- and L-type). 8. In summary, the data show that for neurones in the vesical pelvic ganglia, endothelin causes membrane depolarization and activates an inward current. The ionic mechanisms involve receptor-operated calcium and chloride currents. Also, endothelin causes an initial depression followed by a long-lasting facilitation of the voltage-dependent calcium current.
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PMID:Endothelin modulates calcium channel current in neurones of rabbit pelvic parasympathetic ganglia. 165 45

Ethanol (ETH) and general anesthetics have been reported to facilitate the chloride channel opening, possibly, or at least partly, through an interaction with the GABA-benzodiazepine (BZ) receptor-gated chloride ionophore "supramolecular complex". Recently Ro 15-4513, a novel BZ ligand, has been indicated as a potent and selective antagonist of various ETH-induced behavioral and biochemical effects. However, since its precise characterization is still a matter of debate, we have tested and compared the effect of Ro 15-4513, as well as its antagonism against ETH, in two objective electrophysiological parameters, i.e., the electroencephalograph (EEG) pattern in freely moving rats and single unit activity of reticulata neurons. Ro 15-4513 produced an EEG state of alertness and antagonized the behavioral impairment and the EEG deterioration by ETH. However, while its protective action was consistent against moderate doses (2 g/kg) of ETH, it was much less evident versus higher doses (4 and 8 g/kg). On reticulata cells, Ro 15-4513 potently stimulated their spontaneous firing and reversed the depression by both ETH and Na-pentobarbital. Moreover, the beta-carboline DMCM also had similar effects. The "pure" BZ antagonist Ro 15-1788 was completely inefective against ETH, yet fully cancelled the reversing actions of Ro 15-4513 and DMCM upon ETH or Na-pentobarbital effects. It is concluded that Ro 15-4513 behaves as a BZ inverse agonist, so that its opposition to ETH and Na-pentobarbital is probably the result of its "negative" coupling with the BZ recognition site that triggers the closing of chloride channels. It suggests that BZ inverse agonists might constitute, in the near future, a new class of analeptic drugs.
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PMID:Antagonism of ethanol effects by Ro 15-4513: an electrophysiological analysis. 253 42

Rats exposed to inescapable tailshock exhibit deficits in learning a simple shuttlebox escape task 24 h later. This syndrome has been termed 'behavioral depression' or 'learned helplessness', and is a model of stress-induced depression. In the present study a significant (25%) decrease in GABA receptor-mediated chloride ion flux as measured by muscimol-stimulated 36Cl- uptake in synaptoneurosomes was found in the cerebral cortices of rats that failed the shuttlebox task as compared to naive control rats. Rats which were exposed to tailshock and subsequently learned the escape task did not show a significant difference in muscimol-stimulated 36Cl- uptake as compared to naive control rats. Similarly, rats that failed to learn the shuttlebox escape task had significantly lower in vivo [3H]Ro15-1788 specific binding in cerebral cortex (43%), hippocampus (35%) and striatum (33%) as compared to naive control rats. In cerebellum and hypothalamus, there were significant reductions in specific [3H]Ro15-1788 binding in both animals that failed and animals that learned the shuttlebox escape task as compared to naive controls. To control the stress of the footshock associated with the shuttlebox escape task, we investigated the effect of gridshock in which total footshock received was equivalent to that received by rats who failed the shuttlebox task. There were no differences in muscimol-stimulated 36Cl- uptake or in vivo [3H]Ro15-1788 specific binding between naive controls and rats administered footshock independent of a learning task. These data suggest that the development of stress-induced behavioral depression may be associated with a decrease in GABA receptor-mediated chloride channel function.
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PMID:Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy. 254 50

1. Because hyperbaric pressure profoundly depresses excitatory synaptic transmission, it has proved difficult to account for its excitatory effects in the CNS. We tested the hypothesis that hyperbaric pressure might increase excitation by enhancing facilitation and potentiation during repetitive synaptic activation, and/or by selectively depressing inhibitory synaptic transmission. Intracellular microelectrode recordings were obtained from crustacean muscle fibers innervated by single identifiable excitor and inhibitor motor neurons; the preparations were exposed to pressures of 0.1-10.1 MPa. 2. Hyperbaric pressure reduced the amplitude of the singly evoked excitatory junctional potential (EJP), enhanced paired-pulse facilitation, and increased the potentiation elicited by trains of stimuli. The potentiated EJP at 10.1 MPa approached the comparable response evoked at normobaric pressure. 3. Hyperbaric pressure also depressed inhibitory synaptic transmission, measured as depression of the EJP by the inhibitor motor neuron. However, pressure depressed excitatory and inhibitory synaptic transmission to the same extent. Thus there appears to be no selective effect of pressure on the GABA-activated chloride channel. The amplitude of the inhibited EJP at 10.1 MPa remained below that at normobaric pressure, even during repetitive stimulation. 4. The results do not support the hypothesis that pressure increases central excitation by selectively depressing inhibitory transmission per se; enhancement of potentiation, however, probably plays an important role. In this preparation, in which inhibitory transmission also displays facilitation, pressure did not increase overall excitation or alter the balance between excitation and inhibition. 5. These results predict that a pressure-excitable network should encompass excitatory synaptic connections which exhibit pronounced facilitation and inhibitory synapses with little or no facilitation.
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PMID:Synaptic integrative properties at hyperbaric pressure. 284 2

The potent benzodiazepine receptor ligands beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and the corresponding methylester (beta-CCM) administered i.v. depressed segmental dorsal root potentials in spinal cats, reversed the prolongation of dorsal root potentials by phenobarbitone, and abolished the depression of a motor performance task induced by phenobarbitone in mice; beta-CCE enhanced the low-frequency facilitation of pyramidal population spikes in the hippocampus of anaesthetized rats. These effects of beta-carbolines reflect a depression of GABAergic synaptic transmission and, thus, are diametrically opposed to the enhancing action of benzodiazepine tranquilizers. The specific benzodiazepine antagonist, Ro 15-1788, while not affecting dorsal root potentials, hippocampal population spikes or phenobarbitone-induced motor performance depression, abolished the effects of beta-CCE on the three parameters and similar effects of beta-CCM on the spinal cord and motor performance. A three-state model of the benzodiazepine receptor is proposed in which benzodiazepine tranquilizers act as agonists enhancing the function of the benzodiazepine receptor as a coupling unit between GABA receptor and chloride channel, beta-carbolines act as "inverse agonists" reducing this coupling function, and Ro 15-1788 represents a competitive antagonist blocking both the enhancing effect of agonists and the depressant effect of "inverse agonists" on GABAergic synaptic transmission.
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PMID:A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, beta-carbolines, and phenobarbitone. 613 40

GABA applied by iontophoresis produced GABA-induced currents (GCs) and GABA-induced depolarizations (GDs) which were recorded intracellularly from cat dorsal root ganglia (DRG). Lowering the temperature (37 to 27 degrees C) of the preparation depressed the amplitude of GCs while prolonging their rise-time and decay time. This depressant action was mainly due to a hyperpolarizing shift in the GABA equilibrium potential (EGABA). GABA responses could also be depressed by alkalinization of the superfusion solution or addition of putative chloride pump inhibitors, e.g. SITS, furosemide or bumetanide. However, the mechanism by which these latter procedures depressed GABA responses was not due to a shift in EGABA as occurred with lowered temperature. Instead we suggest that alkalinization or the putative chloride pump inhibitors affect the chloride channel or some other site associated with the GABA receptor complex and cause the depression we observed. GABA responses could be facilitated by lowering the pH of the superfusion solution or by injecting ammonium ion into a DRG. These results suggest that a temperature-sensitive, inwardly directed chloride pump that is resistant to SITS, furosemide or bumetanide, operates in cat DRG.
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PMID:The effects of temperature, pH and Cl-pump inhibitors on GABA responses recorded from cat dorsal root ganglia. 630 67

The central pharmacological effects of ethanol are well known and resemble those of the benzodiazepines (BZD). In addition BZD may interact with ethanol, resulting in enhanced cerebral depression. Ro 15-4513, BZD inverse agonist, potentially antagonizes a lot of effects of ethanol but not all. In our study, another BZD inverse agonist, CGS 8216, reverses the hypnotic effect of ethanol and hypoactivity in mice and rats. CGS 8216 increased also ethanol's locomotor stimulation in mice. This supports the hypothesis that some effects of ethanol are mediated by the GABA-BZD-chloride channel receptor complex. Our behavioural experiments described in this report suggest that CGS 8216, like Ro 15-4513, may act on the alpha-6 subunit of this receptor complex.
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PMID:Influence of CGS 8216 on some acute effects of ethanol. 855 42

Gamma-aminobutyric acid (GABA) acts on pharmacologically and functionally distinct receptors. These sites designated GABA-A and GABA-B receptors, differ with regard to their ionic characteristic and pharmacological properties. The most important distinction is, that the GABA-A receptor is associated with chloride channel and with membrane recognition sites for benzodiazepines. During the past decade numerous studies have made it possible to obtain more detailed knowledge of the structure and properties of the GABA-benzodiazepine receptor complex, which is made up of at least two distinct sites designated as BZD-1 and BZD-2 receptors. Third type, designated as peripheral type is located in the mitochondrial membrane and may regulate a steroidogenesis in the CNS. Molecular cloning studies showed a heterogeneity of GABA-A receptors, which are composed of multiple subunits (alpha, beta, gamma, delta and ro), which form distinct isoreceptors. New classes of GABA-BZD agonists such as zolpidem act selectively upon certain isoreceptors thus showing characteristic pharmacological properties. Recent studies provided detailed information on the interaction of ethyl alcohol (Et-OH) with GABA-BZD receptor complex. The most important finding is, that there are Et-OH sensitive and Et-OH resistant GABA-A receptor isoforms. Recent evidence reinforces the possibility, that reduced activity of the brain GABA-ergic system is associated with mechanism of depression.
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PMID:Recent advances in the GABA-A-benzodiazepine receptor pharmacology. 871 56

The cellular mechanisms that underlie transient synaptic potentiation were studied in visual cortical slices of adult guinea pigs (> or = age 5 wk postnatal). Postsynaptic potentials (PSPs) elicited by stimulation of the white matter/layer VI border were recorded with conventional intracellular techniques from layer II/III neurons. Transient potentiation (average duration 23 +/- 3 min, mean +/- SE) was evoked by 60 low-frequency (0.1 Hz) pairings of weak afferent stimulation with coincident intracellular depolarizing pulses (80 ms) of the postsynaptic cell. Fifty-one percent (47 of 92) of the pairing protocols led to significant enhancement (+26 +/- 3%) of the PSP peak amplitude. Blockade of action potential output from the recorded neuron during pairing with Lidocaine, N-ethyl bromide quaternary salt in the recording micropipette did not reduce the likelihood of potentiation (7 of 14 protocols = 50%). Thus transient synaptic potentiation does not require action potential output from the paired cell or recurrent synaptic activation in the local cortical circuit. Rather, the modification occurs at synaptic sites that directly impinge onto the activated neuron. Intracellular postsynaptic blockade of inhibitory PSPs only onto the paired cell with the chloride channel blocker 4,4'-dinitro-stilbene-2,2'-disulfonic acid and the potassium channel blocker cesium in he micropipette also did not reduce the likelihood of induction of potentiation (6 of 9 protocols = 67%). These results suggest that the potentiation is due to a true upregulation of excitatory synaptic transmission and that it does not require a reduction of inhibitory components of the compound PSP for induction. Chelation of postsynaptic intracellular calcium with 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in all cases effectively blocked the induction of potentiation (no change in the PSP, 9 of 13 protocols; induction of synaptic depression, 4 of 13 protocols), suggesting that a rise in the intracellular postsynaptic calcium level is critical for the pairing-induced synaptic potentiation to occur. Bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) reversibly blocked potentiation of the PSP peak amplitude in most cells (14 of 16) that were capable of significant potentiation of control solution. Blockade of nitric oxide production with bath application of the competitive inhibitor of nitric oxide synthase, L-nitro-arginine (LNA), did not significantly affect the likelihood of synaptic potentiation (11 of 20 cells). It did, however, block subsequent enhancement for several cells (2 of 4) that had previously had their inputs potentiated. Moreover, LNA increased the overall average magnitude of synaptic potentiation (with an additional +28%) when induction was successful. These results suggest that endogenous cortical nitric oxide production can both positively and negatively modulate this NMDA receptor-mediated type of synaptic plasticity.
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PMID:Transient synaptic potentiation in the visual cortex. I. Cellular mechanisms. 908 95


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