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)

Stimulation of the perforant path elicits a behavioral response, wet dog shakes (WDS), and reduction in hippocampal dynorphin A(1-8) immunoreactivity (DYN-IR) and prodynorphin mRNA (DYN mRNA) in rats. This study examined whether glutamate, the proposed endogenous transmitter released by perforant fibers, mediated the above responses. A glutamate antagonist, gamma-D-glutamylglycine (DGG, 25 micrograms/0.5 microliters), or artificial cerebrospinal fluid (ACSF, 0.5 microliters) was injected into the ventral hippocampus 10-20 min prior to acute or daily stimulation of the left perforant path in rats. In acute stimulation experiments, 4 consecutive stimulation trials elicited a total of 73 +/- 4 WDS at an average threshold intensity of 0.46 +/- 0.03 mA in ACSF-treated rats. The hippocampal DYN-IR in these animals decreased by more than 40% in both dorsal and ventral hippocampus relative to sham-stimulated rats. DGG injections significantly elevated the threshold for WDS (0.78 +/- 0.05 mA, P less than 0.01), reduced the number of WDS (45 +/- 6, P less than 0.01), and partially antagonized stimulation-induced reduction of DYN-IR in the ventral, but not dorsal, hippocampus. In daily stimulation experiments, rats received a single trial of stimulation once per day for 6 days. Daily DGG pretreatment almost completely abolished WDS at control threshold intensities, and significantly inhibited stimulation-induced decrease of DYN-IR in both dorsal and ventral hippocampus. In situ hybridization using a 35S-labeled oligodeoxyribonucleotide probe demonstrated a clear depletion of DYN mRNA signal in the dentate granule cell layer of ACSF-treated animals. This depletion was completely prevented in DGG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A glutamate antagonist blocks perforant path stimulation-induced reduction of dynorphin peptide and prodynorphin mRNA levels in rat hippocampus. 168 42

It has been suggested that the maintenance of long-term potentiation (LTP) in the hippocampal mossy fiber (MF) synapse involves a presynaptic mechanism that does not require the activation of protein kinase C (PKC), since this enzyme appears to be absent in the MF presynaptic terminals. In the present study the authors evaluated this proposal by directly comparing the metabolic properties of hippocampal MF synaptosomes and a conventional P2B synaptosomal preparation prepared from the same hippocampal tissue. Protein kinase C-dependent histone phosphotranferase activity was found to be comparable in MF and P2B synaptosomes. Western blot analysis was performed using antisera prepared against four of the PKC isoforms, and the results demonstrate that the alpha, beta, and gamma PKC isoforms are present in relatively equivalent amounts in these two subcellular fractions. However, the cytosolic fraction derived from the hippocampal MF synaptosomes appeared to contain a greater amount of the PKC-epsilon isoform when compared to the P2B synaptosomal preparation. Four distinct endogenous substrates present in the MF synaptosomes are shown to be phosphorylated in response to PKC activation. A functional role for PKC in the hippocampal MF nerve endings seems to be indicated by the finding that 4 beta-phorbol 12,13-dibutyrate (PDBu) and 4 beta-phorbol 12,13-diacetate produce a dose-dependent potentiation of the K(+)-evoked release of endogenous glutamate and dynorphin B, while the inactive 4-alpha-phorbol was without effect. The PDBu-induced enhancement of transmitter release was blocked by the PKC inhibitor, staurosporine. In addition, PDBu significantly facilitated the rise in cytosolic free calcium that immediately followed depolarization of the MF synaptosomal membrane. It is concluded that hippocampal MF presynaptic terminals possess a variety of PKC isoforms and that their activation may have an important facilitory influence on MF synaptic transmission and plasticity.
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PMID:A presynaptic role for protein kinase C in hippocampal mossy fiber synaptic transmission. 168 79

The effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer-344 rats. Young adult (4-month-old) and aged (24-month-old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25-35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1-8)-like immunoreactivity [DYN-A(1-8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN-A(1-8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.
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PMID:Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits. 168 81

The levels of extracellular striatal dopamine and glutamate were measured simultaneously in halothane-anaesthetized rats using microdialysis. Unilateral injections of substance P (0.07 nmol) into the substantia nigra, pars reticulata enhanced the levels of dopamine and glutamate in the ipsilateral striatum. Intranigral injections of neurokinin A (0.09 nmol) enhanced the levels of striatal dopamine, and intranigral injections of gamma-aminobutyric acid (300 nmol) or dynorphin A (0.5 nmol) decreased the levels of striatal dopamine, but none of these had any effect on the levels of striatal glutamate. Local perfusion with the dopamine agonists apomorphine (D1/D2), SKF 38393 (D1) or pergolide (D2) (each at 10(5) M) decreased the levels of striatal dopamine and enhanced the levels of striatal glutamate. In unilateral 6-hydroxydopamine-lesioned rats, basal striatal glutamate levels were decreased bilaterally. Furthermore, on the denervated side intranigral substance P stimulation of striatal glutamate levels was enhanced, while on the intact side intranigral substance P stimulation of striatal dopamine and glutamate levels was similar to that seen in normal rats. These findings suggest that striatonigral substance P provides a stimulatory regulation of ipsilateral striatal glutamate release. Furthermore, it is indicated that striatal glutamate release can also be regulated by dopamine terminals.
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PMID:Striatal dopamine and glutamate release: effects of intranigral injections of substance P. 170 11

The endogenous opioid dynorphin A-(1-17) (Dyn A) has been implicated as a mediator of tissue damage after traumatic spinal cord injury (TSCI) and causes hindlimb paralysis when administered intrathecally. Motor impairment following intrathecal Dyn A is attenuated by antagonists of excitatory amino acids (EAAs); whether opioid receptors mediate such injury has been questioned. TSCI causes various biochemical changes associated with secondary tissue damage, including alterations in tissue amio acids, phospholipids, and fatty acids. Such changes reflect injury severity and correlate with motor dysfunction. The present studies examined whether dynorphin administration causes similar biochemical alterations and whether effects of Dyn A can be modified by treatment with opioid-receptor antagonists. At 24 hr after intrathecal Dyn A, there were significant declines in tissue levels of glutamate, aspartate, and glycine. Increases in total free fatty acids were found at 2 and 24 hr, reflecting changes in both saturated and unsaturated components, which were associated with significant decreases in tissue cholesterol and phospholipid phosphorus at the earlier time point. Each of these neurochemical changes, as well as corresponding motor deficits, were limited by pretreatment with the opioid antagonist nalmefene. In separate experiments, both nalmefene and the selective kappa-opioid antagonist nor-binaltorphimine (nor-BNI) limited dynorphin-induced motor dysfunction; effects of nor-BNI were dose related, and those of nalmefene were stereospecific. Therefore, behavioral and neurochemical consequences of Dyn A administration are mediated in part through opiate receptors, most likely kappa-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynorphin A-(1-17) induces alterations in free fatty acids, excitatory amino acids, and motor function through an opiate-receptor-mediated mechanism. 198 Jan 30

1. In view of the presence of mu, delta and kappa opioid receptors in the spinal dorsal horn and their apparent involvement in behavioural analgesia, the present experiments addressed the action of selective agonists ionophoresed in the vicinity of rat dorsal horn neurones which were located either in lamina I or in laminae III-V. 2. In laminae III-V, kappa agonists (U50488H and dynorphin A) caused a selective inhibition of the nociceptive responses of multireceptive cells, whilst mu and delta agonists [( D-Ala2, MePhe4, Gly-ol]enkephalin and [D-Pen2, D-Pen5]enkephalin respectively) failed to alter either the spontaneous activity or the response to noxious and innocuous cutaneous stimuli and to D,L-homocysteic acid or glutamate. Nocispecific neurones were encountered too rarely in laminae III-V to study their properties. 3. In lamina I, agonists had no effects on either nocispecific or multireceptive neurones. In contrast, the mu agonist [D-Ala2, MePhe4, Gly-ol]enkephalin consistently inhibited nociceptive responses of both multireceptive and nocispecific lamina I cells. The delta agonist [D-Pen2, D-Pen5]enkephalin consistently caused selective inhibition of the nociceptive responses of multireceptive cells but had a mixed profile of action on nocispecific cells. 4. These results suggest that mu, delta and kappa opioid receptors mediate different antinociceptive actions in both laminae III-V and lamina I. The study reveals a distinct physiological role for delta receptors in modulating nociceptive inputs to lamina I neurones. In contrast to mu and kappa receptor actions, delta receptors heterogeneously influence subpopulations of neurones.
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PMID:Distinct antinociceptive actions mediated by different opioid receptors in the region of lamina I and laminae III-V of the dorsal horn of the rat. 217 38

Pressor (VLPA) and depressor (VLDA) areas of the ventrolateral medulla were identified by microinjections of L-glutamate in urethane-anesthetized rats. Cardiovascular effects of opiate agonists microinjected into the same sites were then studied. Agents used to stimulate mu, delta, sigma, kappa, and beta-endorphin (epsilon) receptors were morphiceptin, D-Ala2-D-Leu5-enkephalin, N-allyl-normetazocine, dynorphin, and beta-endorphin, respectively. Opiate receptor stimulation in VLPA decreased blood pressure (BP) and heart rate (HR), while in VLDA it increased BP and HR. Thus, it is the site of injection rather than the type of opiate receptor that determines cardiovascular responses. Naloxone, an opiate antagonist, reversed and prevented these responses. Abolition of cardiovascular responses by spinal transection at the C1 level indicated that the sympathetic nervous system mediated these responses. The following mechanism is proposed for these actions of opiates: Cell bodies in VLPA, but not in VLDA, project to the intermediolateral cell column of the spinal cord. Opiates inhibit VLPA and lower BP and HR by decreasing sympathetic outflow. Opiate-induced inhibition of VLDA, which has an inhibitory effect on VLPA, results in an increase in BP and HR.
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PMID:Cardiovascular responses to medullary microinjections of opiate agonists in urethane-anesthetized rats. 242 96

Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions. 256 86

The K+-evoked release of dynorphin A(1-8)-like immunoreactivity from guinea pig hippocampal mossy fiber synaptosomes was inhibited 53% by L(+)-2-amino-4-phosphonobutyrate (L(+)APB, 300 microM), a glutamate analogue. Equimolar L(+)APB also inhibited the Ca2+-dependent component of endogenous L-glutamate release from these mossy fiber synaptosomes by 40%. The K+-evoked release of both glutamate and dynorphin A(1-8) from rat hippocampal mossy fiber synaptosomes were unaffected by L(+)APB. It is proposed that L(+)APB selectively suppresses the excitatory mossy fiber synaptic inhibiting the Ca2+-dependent release of glutamate and dynorphin A(1-8) from guinea pig but not rat hippocampal mossy fiber terminals.
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PMID:L(+)-2-amino-4-phosphonobutyrate inhibits the release of both glutamate and dynorphin from guinea pig but not rat hippocampal mossy fiber synaptosomes. 257 Jun 25

The binding and internalization of a novel analog of dynorphin-like analgesic basic peptide, [125I]E-2078 (CH3-[125I] Tyr-Gly-Gly-Phe-Leu-Arg-CH3Arg-D-Leu-NHC2H5), by isolated bovine brain capillaries were investigated. High-performance liquid chromatographic analysis showed that no significant metabolism of [125I] E-2078 occurred during incubation with brain capillaries for 30 min at 37 degrees C. The binding of [125I]E-2078 to brain capillaries increased with time and the steady-state cell-to-medium concentration ratio was 58.5 +/- 2.6 microliters/mg of protein. Approximately one-fourth of the [125I]E-2078 binding was resistant to acid wash, and showed significant dependence on temperature and medium osmolarity. The acid sensitive binding of [125I]E-2078, which presumably represents surface binding, was saturable and the Scatchard plot gave a maximal binding capacity Bmax = 147 +/- 29 pmol/mg of protein, and a half-saturation constant (KD) = 4.62 +/- 0.59 microM. Pretreatment of brain capillaries with phenylarsine oxide, an endocytosis inhibitor, completely suppressed the acid resistant binding of [125I]E-2078, but did not influence the surface binding of [125I]E-2078. The acid resistant binding of [125I] E-2078 was inhibited by poly-L-lysine and protamine, but not inhibited by insulin, transferrin, dynorphin (1-8), beta-neoendorphin, naloxone or poly-L-glutamate. Moreover, in vivo brain extraction of [125I]E-2078 in rats was 368 +/- 55% higher than that of [3H] sucrose and was significantly inhibited by 1 mM of unlabeled E-2078. These results demonstrate that E-2078 is internalized by brain capillaries via absorptive-mediated endocytosis, which is a polycation-sensitive pathway.
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PMID:Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E-2078 into the blood-brain barrier. 257 24


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