Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An amino acid, 3,5-dihydroxyphenylglycine (DHPG) induced current responses in Xenopus oocytes expressing a metabotropic glutamate receptor clone mGluR1. Apparent EC50 of DHPG for mGluR1 was slightly lower than that of (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD). DHPG responses were partially inhibited by 2-amino-3-phosphonopropionic acid (AP-3). DHPG had no effect on ionotropic glutamate receptors whose expression was induced in the oocytes following injection of poly(A)+ mRNA of rat brains. In hippocampal slices, DHPG produced slow excitation of pyramidal cells, resulting from a depression of Ca(2+)-dependent K+ current and a voltage-dependent K+ current. These results indicate that DHPG is a specific and potent agonist of mGluRs.
 ...
PMID:3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate receptors. 136 58

We have purified and characterized two vertebrate excitatory amino acid ionotropic receptors from the Xenopus central nervous system. Each is a unitary receptor (i.e., having more than one class of excitatory amino acid agonist specificity within one protein oligomer). The first is a unitary non-N-methyl-D-aspartate (non-NMDA) receptor and the second is a unitary NMDA/non-NMDA receptor. The specific agonist-activated channel activity and pharmacology of each type were recognized by patch-clamping lipid bilayers in which the isolated protein was reconstituted. In the second case, the NMDA and the non-NMDA sites could not be physically separated and exhibited functional interaction. Parallel evidence for this was obtained when poly(A) RNA from Xenopus brain was translated in oocytes: a noncompetitive inhibition of the response to L-kainate is produced by NMDA to a maximum depression of 30% at 1 mM NMDA. Each isolated oligomer contains 42-kDa subunits of the non-NMDA ligand binding type, but the second type has an additional NMDA-receptor-specific 100-kDa subunit. Thus, a subunit-exchange hypothesis can account for the known multiplicity of excitatory amino acid receptor types.
 ...
PMID:Purified unitary kainate/alpha-amino-3-hydroxy-5-methylisooxazole-propionate (AMPA) and kainate/AMPA/N-methyl-D-aspartate receptors with interchangeable subunits. 137 52

The effects of trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) and of DL-2-amino-3-phosphonopropionic acid (AP3), i.e. selective agonist and antagonist of metabotropic quisqualate receptors respectively, on parallel fibre (PF)-mediated EPSPs of Purkinje cells (PCs) were studied in an in vitro slice preparation. Bath application of 500 microM trans-ACPD in conjunction with PF stimulation at 0.2 or 1 Hz depending on the cell always induced a marked depression of PF-mediated EPSPs, which was fully reversible in most cases after wash-out of this compound. Trans-ACPD also often induced a transient depolarization of PCs which induced calcium spike firing in these cells and which again no longer persisted after wash-out of trans-ACPD. Even in cells which were depolarized by trans-ACPD, the decrease in amplitude of PF-mediated EPSPs started before the appearance of calcium spikes, lasted longer than the transient depolarizing effect of trans-ACPD, and was accompanied by no variation in input resistance of the cells when they were manually clamped at their initial resting potential. Bath application of 600 microM DL-AP3 had no effect on PF-mediated EPSPs or the bioelectrical activities of PCs. Moreover, it did not prevent the effects of trans-ACPD mentioned before. The present results are not consistent with the view that coactivation of ionotropic and metabotropic quisqualate receptors of PCs is sufficient to induce a long-term depression of PF-mediated EPSPs.
 ...
PMID:Effects of ACPD and AP3 on parallel-fibre-mediated EPSPs of Purkinje cells in cerebellar slices in vitro. 166 80

Glutamate (GLU) mediates its 'fast' excitatory transmitter action in the brain by directly gating cation-selective ion channels ('ionotropic' receptors). However, GLU can also activate another type of receptor, coupled to phospholipase C ('metabotropic' receptor). In hippocampal cells, stimulation of this metabotropic receptor by GLU, or by a racemic mixture of (1S-3R and 1R-3S) 1-aminocyclopentyl-1,3-dicarboxylate (ACPD), induces a slower excitation mediated by inhibition of K+ currents. We have assessed whether this slow form of metabotropic receptor excitation can contribute to the effects of synaptically released GLU in hippocampal slice cultures, by recording the responses of CA3 pyramidal cells to afferent mossy fibre stimulation. When the fast ionotropic response was blocked pharmacologically, mossy fibre stimulation produced a slow depolarizing postsynaptic potential associated with a decrease in membrane conductance, a depression of the slow after-hyperpolarization following a train of action potentials, and reduced accommodation during the action potential train. Under voltage-clamp, mossy fibre stimulation produced a slow voltage-dependent inward current which resembled that produced by application of exogenous ACPD or quisqualate (QUIS), and which was occluded by these metabotropic agonists. We therefore suggest that synaptically released GLU can induce two types of postsynaptic responses: a fast excitation through activation of ionotropic receptors and a slower excitation associated with inhibition of K+ conductances through activation of metabotropic receptors. This is analogous to the dual action of acetylcholine on ionotropic (nicotinic) and metabotropic (muscarinic) receptors.
 ...
PMID:Glutamate mediates a slow synaptic response in hippocampal slice cultures. 167

Cerebellar long-term depression (LTD) is a model of synaptic plasticity in which conjunctive stimulation of parallel fiber and climbing fiber inputs to a Purkinje neuron induces a persistent depression of the parallel fiber-Purkinje neuron synapse. We report that an analogous phenomenon may be elicited in the cultured mouse Purkinje neuron when iontophoretic glutamate application and depolarization of the Purkinje neurons are substituted for parallel fiber and climbing fiber stimulation, respectively. The induction of LTD in these cerebellar cultures requires activation of both ionotropic (AMPA) and metabotropic quisqualate receptors, together with depolarization in the presence of external Ca2+. This postsynaptic alteration is manifest as a depression of glutamate or AMPA currents, but not aspartate or NMDA currents. These results strengthen the contention that the expression of cerebellar LTD is at least in part postsynaptic and provide evidence that activation of both ionotropic and metabotropic quisqualate receptors are necessary for LTD induction.
 ...
PMID:A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. 167 95

Activation of metabotropic glutamate receptors (mGluRs, QP or ACPD receptors) has recently been shown to cause depolarization, blockade of the slow after-hyperpolarization and depression of calcium currents in hippocampal pyramidal cells. Here, we report evidence for a new mGluR-mediated effect: slowing of the spike repolarization in CA1 cells in rat hippocampal slices. During blockade of the ionotropic glutamate receptors, the mGluR agonists trans-1-amino-cyclopentyl-1,3-dicarboxylate (t-ACPD), quisqualate or L-glutamate caused spike broadening. In contrast, the ionotropic receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) was ineffective. The spike broadening may act in concert with the other mGluR effects, e.g. by further increasing the influx of Ca2+ ions which, in turn, may contribute to synaptic modulation.
 ...
PMID:Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons. 168 72

Excitatory amino acids mediate fast synaptic transmission in the central nervous system through the activation of at least three distinct ionotropic receptors: N-methyl-D-aspartate (NMDA), the alpha-amino-3-hydroxy-5-methyl-isoxasole-4-propionate (AMPA)/quisqualate (QUIS) and the kainate subtypes (for reviews, see refs 1, 2). They also activate the additional QUIS 'metabotropic' receptor (sensitive to trans-1-amino-cyclopentyl-1,3-dicarboxylate, ACPD) linked to inositol phospholipid metabolism. We have used hippocampal slice cultures to study the electrophysiological consequences of the metabotropic response. We find that activation of an ACPD-sensitive QUIS receptor produces a 'slow' excitation of CA3 pyramidal cells, resulting from depression of a Ca2(+)-dependent K+ current and a voltage-gated K+ current. Combined voltage-clamp and microfluorometric recordings show that, although these receptors can trigger an increase in intracellular Ca2+ concentration, suppression of K+ currents is independent of changes in intracellular Ca2+. These effects closely resemble those induced by activating muscarinic acetylcholine receptors in the same neurons and suggest that excitatory amino acids not only act as fast ionotropic transmitters but also as slow neuromodulatory transmitters.
 ...
PMID:Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters. 217 30

Cerebellar Purkinje neurons possess AMPA ((RS)-alpha-amino-3-hydroxyl-5- methyl-4-isoxazolepropionic acid)-sensitive ionotropic glutamate receptors (AMPA GluRs) and ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid)-sensitive metabotropic glutamate receptors (mGluRs). The contributions of these receptors to responses elicited by dual receptor activation in cultured cerebellar Purkinje neurons were delineated by quantitative analysis of agonist-induced single unit activity. Responses to co-activation using Quis or AMPA + ACPD were biphasic, consisting of a dramatic increase in firing rate (excitatory phase) followed by a temporary decrease (inhibitory phase). In half of the cells tested bursting was induced during both the excitatory and inhibitory phases and the duration of each phase was prolonged relative to responses observed in non-bursting cells. Quantitative comparisons of these responses and responses produced by selective activation of AMPA GluRs and mGluRs revealed that: (a) AMPA GluRs mediated the dramatic changes in firing rate, (b) mGluRs mediated the dramatic increases in bursting and the extended duration of each phase and (c) these AMPA GluR and mGluR mediated effects were largely additive when simultaneously activated. Nevertheless, interactions did occur with repeated co-activation of AMPA GluRs and mGluRs, as indicated by selective changes in the mGluR-mediated bursting component of the response. Such modulation may contribute to synaptic regulation of Purkinje neuron excitability, for example, that associated with long term depression.
 ...
PMID:Ionotropic and metabotropic components of electrophysiological response of cerebellar Purkinje neurons to excitatory amino acids. 750 90

Whole-cell recording techniques were used to record isolated slow inhibitory postsynaptic currents in CA1 pyramidal neurons from rat hippocampal slices. Application of 6-cyano-7-nitroquinoxaline-2,3-dione and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid eliminated excitatory synaptic transmission, resulting in a 38% reduction in slow inhibitory postsynaptic current magnitude. Subsequent addition of the GABAA antagonist picrotoxin caused a further decrease in slow inhibitory postsynaptic current amplitude. The remaining, isolated slow inhibitory postsynaptic current was blocked by the GABAB antagonist 2-hydroxysaclofen and when cesium was substituted for intracellular potassium. The kinetics of isolated slow inhibitory postsynaptic currents were characterized by single exponential, fourth power activation, and double exponential inactivation. These slow inhibitory postsynaptic currents had a reversal potential of -85.7 +/- 1.6 mV, and a slope conductance of 935 +/- 277 pS. Single slow inhibitory postsynaptic currents carried a total charge flux of 13.4 +/- 7.6 pC. Repetitive stimulation up to 1 Hz progressively reduced steady-state slow inhibitory postsynaptic current amplitude. This attenuation was characterized by a decrease in slope conductance, but slow inhibitory postsynaptic current reversal potential remained unchanged, as did slow inhibitory postsynaptic current kinetics. These results indicate that, under physiological conditions, both ionotropic glutamate- and GABAA-mediated transmission contribute to slow inhibitory postsynaptic current recruitment. Given this finding, activity-dependent decreases in GABAA transmission could contribute to slow inhibitory postsynaptic current depression, though not exclusively, since isolated slow inhibitory postsynaptic currents also demonstrated this property. The use-dependent depression of isolated slow inhibitory postsynaptic currents may be a consequence of a reduction in transmitter release.
 ...
PMID:Properties of isolated GABAB-mediated inhibitory postsynaptic currents in hippocampal pyramidal cells. 753 98

The rhythmical local ionophoretic applications of acetylcholine (ACh) to the somatic membrane of Helix lucorum identified neurons evokes the reversible depression of the ACh-induced response which shows cholinoreceptor (ChR) desensitization. ChR desensitization is regulated not by one but by several known second messengers and G-proteins. The endogenous opioids perform the excitation or inhibitory tonic control of the membrane potential in some neurons constantly activating the ionotropic opiate receptors. The direction of neuron ChR desensitization modulation by opioids depends on the type of the activated modulatory opiate receptors (mu or kappa) on the neuron membrane. Second messengers are involved in intracellular mechanism of modulation of the ChR desensitization by opiate kappa-agonist bremazocine.
 ...
PMID:Regulation of neuron cholinoreceptor plasticity of Helix lucorum by second messengers and opioids. 759 72


1 2 3 4 5 6 7 8 9 10 Next >>