Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:6893-26-1 (glutamate)
 73,096 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal peptides exert neurohormonal and neurotransmitter (neuromodulator) functions in the central nervous system (CNS). Besides these functions, a group of neuropeptides may have a capacity to create cell proliferation, growth, and survival. Axotomy induces transient (1-21 d) upregulation of synthesis and gene expression of neuropeptides, such as galanin, corticotropin releasing factor, dynorphin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, cholecystokinin, angiotensin II, and neuropeptide Y. These neuropeptides are colocalized with "classic" neurotransmitters (acetylcholine, aspartate, glutamate) or neurohormones (vasopressin, oxytocin) that are downregulated by axotomy in the same neuronal cells. It is more likely that neuronal cells, in response to axotomy, increase expression of neuropeptides that promote their survival and regeneration, and may downregulate substances related to their transmitter or secretory activities.
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PMID:Neuropeptide messenger plasticity in the CNS neurons following axotomy. 757 12

Adrenal steroid and stress effects were determined in hippocampus on levels of dynorphin (DYN) mRNA, expressed in dentate gyrus, and excitatory amino acid receptors, measured in Ammon's horn and dentate gyrus. Adrenalectomy (ADX) decreased DYN mRNA levels in dentate gyrus and replacement with aldosterone (ALDO), a specific type I adrenal steroid receptor agonist, prevented the decrease. Ru28362, a specific type II receptor agonist, had no effect. Likewise, kainate receptor binding to the stratum lucidum and hilus region of dorsal hippocampus was decreased after ADX and this decrease was prevented by ALDO but not by Ru28362 treatment. Similar though smaller effects were found for CNQX binding to AMPA receptors but only in the dentate gyrus molecular or infra- and supragranular layers. Although corticosterone (CORT) treatment of intact rats (40 mg/kg for 3 weeks) elevated DYN mRNA levels in dentate gyrus, up to 14 days of daily restraint stress (1 or 6 h/day) had no significant effect. Neither CORT treatment nor repeated restraint stress altered NMDA and non-NMDA glutamate receptors in hippocampus. The results of this study showing ADX-induced decreases of DYN mRNA and CNQX binding in dentate gyrus and decreased kainate binding in mossy fiber terminal regions are consistent with morphological evidence showing that adrenal steroids maintain normal integrity and structure of dentate gyrus neurons and do so via type I adrenal steroid receptors. These same parameters are apparently not sensitive to chronic restraint stress although the effects of other stressors must be examined.
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PMID:Effects of adrenal steroid manipulations and repeated restraint stress on dynorphin mRNA levels and excitatory amino acid receptor binding in hippocampus. 766 79

Hippocampal mossy fiber (MF) nerve endings may be isolated in a subcellular fraction (P3) that releases both prodynorphin-derived peptides and glutamate (Glu) in a calcium-dependent manner when depolarized. However, this isolation procedure does not yield a pure preparation of MF synaptosomes. The present study evaluates the proportion of dynorphin (Dyn) and Glu that is released from synaptosomes in the P3 fraction that are of MF origin. We have addressed this issue by determining the degree to which a selective lesion of the dentate granule cell/MF system in vivo concomitantly reduces the exocytosis of Dyn and Glu from the P3 subcellular fraction. Unilateral injections of colchicine into the dentate gyrus resulted in a substantial and selective degeneration of the granule cell/MF pathway in the rat hippocampal formation. The overall integrated density of the Timm-stained band, which corresponds to the position of the MF terminal field, was estimated to be reduced by 75%. After this extensive loss of MF boutons, the K(+)-evoked release of Dyn and Glu from the P3 fraction was reduced by 95 and 51%, respectively. The loss of Timm staining and evoked Dyn release indicate that colchicine effectively eliminated MF synaptosomes from the P3 fraction. Those subcellular entities that were not destroyed by colchicine comprised approximately 50% of the protein and evoked Glu release measured by using the P3 fraction. In addition, the present results demonstrate that the inhibitory potency of the kappa opioid agonist U-50,488H was not altered by the elimination of MF boutons from this synaptosomal preparation. This finding indicates that U-50, 488H is capable of suppressing Glu exocytosis from both MF and non-MF synaptosomes. These results are consistent with the hypothesis that Dyn peptides and Glu are co-released from hippocampal MF terminals.
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PMID:Evidence for the corelease of dynorphin and glutamate from rat hippocampal mossy fiber terminals. 768 56

High doses of stimulants of abuse, such as methamphetamine and cocaine, cause significant increases in the content of neurotension- and dynorphin-like immunoreactivity in the striatum and nucleus accumbens (approximately 200-600% of control) in the rat. These changes in neuropeptide content are caused by stimulation of dopamine D1 receptors and prevented by the glutamate NMDA receptor antagonist, MK 801. Stimulation of the NMDA receptor with N-methyl-D-aspartate results in increases in the neuropeptide levels like that caused by methamphetamine and cocaine. These findings demonstrate that stimulants of abuse profoundly influence neurotensin and dynorphin pathways associated with extrapyramidal and limbic structures by an interaction of activated dopamine D1 and glutamate NMDA receptors.
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PMID:The role of NMDA receptor systems in neuropeptide responses to stimulants of abuse. 775

Recent evidence has demonstrated that N-methyl-D-aspartic acid (NMDA) and non-NMDA, excitatory amino acid (EAA) receptor antagonists block the motor stimulating, neurotoxic, and rewarding actions of cocaine and the amphetamines. The participants in this symposium discussed evidence that (i) the initiation of stimulant-induced behavioral sensitization involves NMDA receptor stimulation in the ventral tegmental area (VTA), (ii) competitive and non-competitive NMDA antagonists block the dopaminergic neurotoxic actions of methamphetamine, and (iii) NMDA receptor antagonists block cocaine and methamphetamine-induced increases in striatal neurotensin and dynorphin expression. Furthermore, a theoretical framework was proposed in which to interpret dopamine-glutamate interactions based on tonic and phasic dopamine release in the striatum under acute, chronic and withdrawal states of stimulant exposure.
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PMID:Introduction to the role of excitatory amino acids in the actions of abused drugs: a symposium presented at the 1993 annual meeting of the College on Problems of Drug Dependence. 775 7

Sulphated cholecystokinin-8 (CCK-8) given into the neostriatum of the rat by in vivo microdialysis produced a concentration-dependent (1-100 microM) increase in extracellular aspartate (Asp) and dynorphin B (Dyn B), but not in glutamate, GABA or dopamine levels. The increase in Asp levels produced by 10 microM CCK-8 was approximately 10 fold and was inhibited (approximately 50%) by the CCKB antagonist L-365,260 (20 mg kg-1, i.p.), while the increase in Dyn B (approximately 2 fold) was totally abolished. Both increases were inhibited (approximately 50%) by local infusion of 10 microM of tetrodotoxin (TTX). Thus, CCK exerts modulatory effects in the basal ganglia, possibly by interacting with local neostriatal neurones releasing Asp, and with Dyn B-containing neurones projecting to the pars reticulata of the substantia nigra.
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PMID:Modulation of striatal aspartate and dynorphin B release by cholecystokinin (CCK-8) studied in vivo with microdialysis. 788 Oct 50

In the corpus striatum and nucleus accumbens, neuropeptides participate along with conventional neurotransmitters such as dopamine, gamma-aminobutyric acid (GABA), acetylcholine and glutamate in the regulation of locomotor activity, stereotyped motor behaviors and neural events related to reward and affective state. The present review concerns itself with four major neuropeptide systems--enkephalin, dynorphin, tachykinins and neurotensin--and it summarizes neuroanatomical and functional studies as well as emphasizing regulatory interactions between neurotransmitters and neuropeptides at the level of neuropeptide gene expression. Dopaminergic transmission emanating from midbrain dopaminergic cell bodies of the substantia nigra and the ventral tegmentum regulates striatal and accumbens neuropeptide levels and their mRNAs. Evidence is presented for D1 or D2 receptor involvement as well as D1-D2 interactions that modulate neuropeptide and mRNA levels in striatum and accumbens neurons. Regulatory influences by GABAergic, serotonergic and cortical (glutamatergic) neurotransmission and via sigma receptors and circulating adrenal steroids are also described. The evidence gathered in many laboratories thus far indicates that these major basal ganglia peptidergic systems are modulated dynamically and sometimes in opposing ways by various neurochemical inputs which alter neuropeptide and neuropeptide mRNA levels over both short- and long-term. Neuropeptide systems are involved in the regulation and execution of motor programs and may also be involved in the control of mood and affect as well as self-administration behavior and behavioral sensitization, especially via the nucleus accumbens and its reciprocal connections with the midbrain, hippocampus and frontal cortex. Glucocorticoids modulate mood as well as self-administration behavior and influence locomotor activity and certain forms of stereotypy. The modulation of striatal proenkephalin and protachykinin mRNA levels by adrenal steroids is described along with distribution of adrenal steroid receptor subtypes. Adrenal steroid regulation of neuropeptide gene expression in striatum, accumbens and midbrain suggests that there may be a wider role for glucocorticoids and for other neuropeptide systems in environmental and drug influences on normal and abnormal behaviors involving the nigrostriatal and mesolimic systems.
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PMID:Molecular aspects of neuropeptide regulation and function in the corpus striatum and nucleus accumbens. 790 70

Dynorphin A reduced lumbosacral blood flow, elevated cerebrospinal fluid lactic acid concentrations and caused flaccid hindlimb paralysis and striking neuropathological changes after its injection into the spinal subarachnoid space in rats. Coadministration of the vasodilator hydralazine substantially eliminated the paralytic, anaerobic metabolic and neuropathological responses to dynorphin A. In contrast, in concentrations up to 1 mM, dynorphin A did not alter the viability of cultured rat spinal cord neurons. Thus, it appears that this peptide lacks direct neurotoxic effects and that neuronal injuries in vivo result primarily from ischemia associated with dynorphin A-induced blood flow reductions. NMDA receptor antagonists significantly improved recovery from dynorphin A-induced hindlimb paralysis, and substantially eliminated neuropathological changes without attenuating the acute blood flow reductions or lactic acid elevations. Additionally, glutamate and aspartate concentrations were increased significantly in spinal cord cerebrospinal fluid samples removed during the time that peptide-induced spinal cord blood flow reductions were observed. In contrast, neither amino acid concentration was elevated in media removed after 1-hr exposure of spinal cord neuronal cell cultures to 100 microM concentrations of dynorphin A. These results indicate that the paralysis and spinal cord injuries produced in rats after spinal subarachnoid injection of dynorphin A result predominantly from spinal cord ischemia, and further identify excitatory amino acids and N-methyl-D-aspartate receptor mechanisms as important mediators in this injury model.
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PMID:Dynorphin A-induced rat spinal cord injury: evidence for excitatory amino acid involvement in a pharmacological model of ischemic spinal cord injury. 790 61

We examined the effects of agonists at mu, delta and kappa opioid receptors on neurons located in the nucleus tractus solitarius of the rat using whole-cell patch-clamp recordings in brainstem slices. The mu selective opioid agonist DAMGO hyperpolarized most neurons tested. This effect was associated with the activation of a K(+)-conductance. The effect of DAMGO tended to desensitize and was blocked by naloxone. Dynorphin A also produced this effect. However, the kappa-1-selective opioid agonist U-69593 and two delta-selective opioid agonists did not. DAMGO also depressed glutamate-mediated excitatory postsynaptic potentials and GABA-mediated evoked by stimulation of the tractus solitarius. Dynorphin A, U-69593 and delta-opioid agonists also reduced the excitatory postsynaptic potential, although they were less effective than DAMGO. The presynaptic inhibitory effects of DAMGO were also blocked by naloxone, but did not desensitize. These actions may help to explain the ability of opiates to modulate a variety of autonomic reflexes.
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PMID:Selective opioid agonists modulate afferent transmission in the rat nucleus tractus solitarius. 809 53

The mossy fibre pathway in the hippocampus uses glutamate as a neurotransmitter, but also contains the opioid peptide dynorphin. Synaptic release of dynorphin causes a presynaptic inhibition of neighbouring mossy fibres and inhibits the induction and expression of mossy fibre long-term potentiation. These findings demonstrate a physiological role for a neuropeptide in the central nervous system, provide a functional basis for the coexistence of a neuropeptide with classic neurotransmitters and demonstrate the very different roles played by these two classes of signalling molecules.
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PMID:The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. 809 24


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