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)

Bath application of the muscarinic receptor agonist, muscarine, produced a concentration-dependent depression of synaptic activity in the dentate gyrus of hippocampal slices. A concentration of 10 microM muscarine produced a reversible depression that could be competitively antagonized by the muscarinic receptor antagonist pirenzepine. However, other muscarinic receptor subtype (M1-M3) antagonists could also block the effects of muscarine. The rank order of antagonist potency was: 4-diphenylacetoxy-N-methyl-piperidine methiodide (M3/M1 antagonist) > pirenzepine (M1) > AFDX-116 (M2). The depression produced by 10 microM muscarine was not affected by in vivo pretreatment with pertussis toxin, and therefore was not mediated by a pertussis toxin-sensitive G-protein. In addition, high concentrations of muscarine did not affect either basal or isoproterenol-stimulated accumulation of cyclic AMP from slices of dentate gyrus. Muscarine also produced a concentration-dependent blockade of the induction of norepinephrine-induced long-lasting potentiation in the dentate gyrus. Norepinephrine-induced long-lasting potentiation is a form of long-lasting plasticity induced in medial perforant path synapses by beta-adrenergic agonists such as isoproterenol. The muscarinic blockade of norepinephrine-induced long-lasting potentiation was also prevented by pretreatment with pirenzepine. Based on these pharmacological data, we conclude that muscarinic depression of evoked responses, as well as blockade of norepinephrine-induced long-lasting potentiation, involves activation of either M3 or M1, but not M2, muscarinic receptors. These data also demonstrate that in addition to modulating normal synaptic transmission, muscarinic receptors may also play an important role in modulating synaptic plasticity.
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PMID:Muscarinic depression of synaptic transmission and blockade of norepinephrine-induced long-lasting potentiation in the dentate gyrus. 768 52

1. The effects of adenosine were studied in cultured frog melanotrophs by the patch-clamp technique. 2. In cell-attached experiments, most cells responded to adenosine (50 microM) by a reversible inhibition of action current discharges without any apparent desensitization. 3. In whole-cell experiments, adenosine provoked a hyperpolarization accompanied by a depression of spontaneous action potentials and a decrease in membrane resistance. When adenosine was repeatedly applied, tachyphylaxis was observed. Addition of GTP (100 microM) in the intracellular solution augmented the percentage of cells hyperpolarized by adenosine, and the duration and amplitude of the hyperpolarization, and prevented the tachyphylaxis. 4. Pretreatment with pertussis toxin (1 microgram ml-1) blocked adenosine-induced inhibition. 5. In cells dialysed with the non-hydrolysable GTP analogue GTP gamma S (100 microM), adenosine caused a sustained, strong hyperpolarization and an irreversible inhibition of spikes. 6. The effect of adenosine was mimicked by the A1 receptor agonist R-PIA (R-N6-phenylisopropyl-adenosine; 50 microM) and blocked by the A1 receptor antagonist CPDPX (8-cyclopentyl-1,3-dipropylxanthine, 50 microM). The A2 receptor antagonist CGS15943 (9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5-c] quinazoline-5-imine; 50 microM) did not affect the adenosine-induced response. 7. The results suggest that, in frog melanotrophs, adenosine exerts a direct hyperpolarizing effect accompanied by blockage of spontaneous action potentials. The effect of adenosine is mediated through A1 receptors coupled to a Gi/o protein.
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PMID:Inhibitory effect of adenosine on electrical activity of frog melanotrophs mediated through A1 purinergic receptors. 773 30

1. An in vitro slice preparation of rat amygdala was used to study the paired-pulse depression of the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential e.p.s.p.NMDA. 2. The e.p.s.p.NMDA was isolated pharmacologically by applying a solution containing the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the gamma-aminobutyric acidA (GABAA) blocker picrotoxin and increasing the stimulus intensity. 3. When two stimuli of identical strength were applied in close succession, the second e.p.s.p.NMDA was depressed. This paired-pulse depression was seen with interstimulus intervals of between 100 ms and 2000 ms; the maximal depression was observed at interval of 200 ms. 4. Superfusion of phaclofen or 2-hydroxy-saclofen inhibited the paired-pulse depression indicating the involvement of GABAB receptors. 5. Bath applications of Ba2+ or intracellular injection of Cs+ to block post- but not presynaptic GABAB receptors failed to inhibit the paired-pulse depression (PPD). 6. Incubation of slices with pertussis toxin prevented the postsynaptic hyperpolarization induced by baclofen. The PPD of e.p.s.p.NMDA, however, was not affected by pertussis toxin treatment. 7. These results suggest that GABA released by the first stimulus acts on GABAB receptors to suppress the second e.p.s.p.NMDA via mechanisms other than activation of a postsynaptic GABAB receptor-coupled K+ conductance.
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PMID:Paired-pulse depression of the N-methyl-D-aspartate receptor-mediated synaptic potentials in the amygdala. 785 45

1. Whole cell voltage-clamp techniques were used in the CA1 region of rat hippocampal slices to study presynaptic and postsynaptic gamma-aminobutyric acid B (GABAB) response mechanisms. The effects of the protein kinase C activator phorbol 12,13-diacetate (PDA), barium (Ba2+), and pertussis toxin were compared on the presynaptic and postsynaptic GABAB actions of bath-applied baclofen and paired-pulse depression (PPD) of the monosynaptic GABAA inhibitory postsynaptic current (IPSC). The magnitude of PPD was dependent on the amplitude of the first response. PPD was predominantly a GABAB-mediated effect, as it was very much reduced by the GABAB antagonist CGP 35348. 2. PDA enhanced monosynaptic GABAA IPSCs through an apparently presynaptic mechanism. Iontophoretic GABAA responses were unaffected, and there was no change in EIPSC. PDA increased the frequency of spontaneous, tetrodotoxin-insensitive IPSCs without significantly affecting their amplitudes. The inactive phorbol ester, 4 alpha-PDA did not alter IPSCs. After PDA application, stimulus intensity was adjusted to produce responses of comparable amplitude to control responses. PDA had a marked and reversible depressant effect on the postsynaptic GABAB response and caused a lesser, but still significant, reduction in the baclofen-induced reduction of monosynaptic IPSCs. PDA had no effect on PPD. 3. Ba2+ dramatically reduced postsynaptic GABAB responses; it had no effect on PPD. Ba2+ tended to decrease the presynaptic baclofen reduction of IPSCs, although this was not statistically significant. 4. Pertussis toxin, injected 2-3 days earlier into the intact hippocampus, blocked all three GABAB responses equally (approximately 70% decrease). 5. We conclude that presynaptic and postsynaptic GABAB mechanisms are mediated by G proteins that couple to different mechanisms. Discrepancies with previous work are evidently due to the use of different tissue preparations and different target responses. Even though protein kinase C activation caused a partial reduction in the presynaptic effect of baclofen, its lack of effect on PPD makes a significant role for protein kinase C in modulation of PPD unlikely.
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PMID:Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells. 788 61

This study describes the depression of calcium currents caused by activation of human D3 dopamine receptors which have been stably expressed in the neuroblastoma x glioma NG108-15 cell line. Transfected cells, which had been differentiated with prostaglandin E1 and isobutylmethylxanthine, exclusively expressed D3 receptor mRNA, which was demonstrated by reverse transcription polymerase chain reaction techniques. Transfected cells had high affinity binding sites for iodosulpiride, with a Kd of 0.8 nM and receptor density of 240 fmol mg-1 protein. Calcium currents were recorded using nystatin-perforated patch clamp techniques. In contrast to untransfected cells that had been differentiated, high-threshold calcium currents in differentiated hD3-NG108-15 cells were depressed by application of dopamine and quinpirole. These responses were abolished by the dopamine receptor antagonist S-(-)-sulpiride (1 microM), demonstrating that they were caused by the activation of the transfected dopamine receptors. Coupling of human D3 receptors to calcium currents was sensitive to the action of pertussis toxin, suggesting the involvement of G-proteins of the Gi and/or G(o) subtype. These results demonstrate that human D3 receptors represent a functional class of dopamine receptor.
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PMID:Functional expression of human D3 dopamine receptors in differentiated neuroblastoma x glioma NG108-15 cells. 791 12

1. Rat cultured ventromedial hypothalamic (VMH) neurones obtained from embryonic hypothalamus were used to study the muscarinic (carbachol) modulation of voltage-gated K+ currents with the whole-cell patch-clamp technique. 2. Carbachol produced a potent and concentration-dependent (100 fM to 100 microM) decrease of the outward delayed rectifier K+ current (IK) with an IC50 of 44 pM and a Hill coefficient of 0.4. The carbachol-induced depression of IK was reduced by pirenzepine (1-10 microM) and atropine (1 microM). Carbachol had no effect on the transient outward K+ current (IA). 3. Intracellular dialysis with guanosine 5'-O-(2-thiodiophosphate) (GDP-beta-S, 500 microM) significantly diminished the carbachol-induced depression of IK, suggesting GTP-binding protein (G-protein) involvement. Pre-incubation of VMH neurones with pertussis toxin (200-400 ng ml-1) or cholera toxin (1 microgram ml-1) for 24-48 h had no effect on the carbachol-induced depression of IK. This suggested that the G alpha o, G alpha i, and G alpha s G-protein alpha-subunits were not involved in mediating the carbachol-induced depression of IK in VMH neurones. 4. Treatment (24-48 h) of VMH neurones with antisense phosphothio-oligodeoxynucleotides to the G alpha 11 G-protein subunit (10 microM) significantly diminished the carbachol-induced depression of IK. Treatment with 10 microM of either G alpha 11 sense or antisense to G alpha q had no effect. 5. These results demonstrate a novel and potent muscarinic depression of IK in VMN neurones, and that this depression is specifically mediated by the G alpha 11 G-protein subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarine modulation by a G-protein alpha-subunit of delayed rectifier K+ current in rat ventromedial hypothalamic neurones. 801 94

Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.
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PMID:Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. 813 77

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

A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice. The depression of liver drug metabolism by a cellular vaccine containing a mutated pertussis toxin was less marked than that induced by the wild-type vaccines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine had a less marked effect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not affect liver drug metabolism, indicating a role of the whole bacterial cell in this side effect. All the cellular vaccines studied induced high serum interleukin-6 levels; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the whole bacterial cell is also important for interleukin-6 induction. All vaccines studied were very poor tumor necrosis factor inducers.
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PMID:Depression of liver metabolism and induction of cytokine release by diphtheria and tetanus toxoids and pertussis vaccines: role of Bordetella pertussis cells in toxicity. 826 41

1. The electrophysiological action of the mu-opioid receptor-preferring agonist D-Ala2, MePhe4, Met(O)5-ol-enkephalin (FK 33-824) on synaptic transmission has been studied in area CA3 of organotypic rat hippocampal slice cultures. 2. FK 33-824 (1 microM) had no effect on the amplitude of pharmacologically isolated N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated EPSPs. 3. FK 33-824 (10 nM to 10 microM) reduced the amplitude of monosynaptic inhibitory postsynaptic potentials (IPSPs) that were elicited in pyramidal cells with local stimulation after pharmacological blockade of excitatory amino acid receptors. This effect was reversible, dose-dependent, and sensitive to naloxone and the mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP). FK 33-824 at 1 microM caused a mean reduction in the amplitude of the monosynaptic IPSP of 70%. 4. Neither delta- nor kappa-receptor-preferring agonists had any effect on excitatory or inhibitory synaptic potentials. 5. The disinhibitory action of FK 33-824 was blocked by incubating the cultures with pertussis toxin (500 ng/ml for 48 h) or by stimulation of protein kinase C with phorbol 12,13-dibutyrate (PDBu, 0.5 microM). 6. The depression of monosynaptic IPSPs by FK 33-824 was unaffected by extracellular application of the K+ channel blockers Ba2+ or Cs+ (1 mM each). 7. FK 33-824 produced a decrease in the frequency of miniature, action potential-independent, spontaneous inhibitory synaptic currents (mIPSCs) recorded with whole-cell voltage-clamp techniques, but did not change their mean amplitude. Application of the Ca2+ channel blocker Cd2+ (100 microM) or of nominally Ca(2+)-free solutions did not alter either the frequency and amplitude of mIPSCs or the reduction of mIPSC frequency induced by FK 33-824. 8. The effect of FK 33-824 on spontaneous mIPSCs was prevented by naloxone, and by incubation of cultures with pertussis toxin. 9. These results indicate that mu-opioid receptors decrease GABA release presynaptically by a G protein-mediated inhibition of the vesicular GABA release process, and not by changes in axon terminal K+ or Ca2+ conductances that are sensitive to extracellular Ba2+, Cs+ or Cd2+.
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PMID:Mechanism of mu-opioid receptor-mediated presynaptic inhibition in the rat hippocampus in vitro. 830 42

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