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Query: CAS:6893-26-1 (glutamate)
 73,096 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurotoxic amino acids beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) were evaluated for possible effects on spontaneous and stimulus-evoked release of L-glutamate (L-Glu) and dynorphin A(1-8)-like immunoreactivity (LI) from guinea pig hippocampal mossy fiber synaptosomes. BOAA (200 microM), but not BMAA (1 mM), was found to significantly increase both basal cytosolic and KCl-stimulated vesicular release of L-Glu. Neither BOAA nor BMAA had any effect on dynorphin A(1-8)-LI release from these synaptosomes. This is the first report describing a presynaptic facilitatory action of BOAA upon L-Glu release; an effect which may contribute to the neurotoxic properties of this proposed environmental toxin.
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PMID:BOAA selectively enhances L-glutamate release from guinea pig hippocampal mossy fiber synaptosomes. 257 28

The effects of the microiontophoretic application of dynorphin A-(1-13) (DYN 13) and the benzomorphans ethylketocyclazocine (EKC), bremazocine and MRZ 2549, (kappa) opioid agonists, and of morphine and morphiceptin, (mu) opioid agonists, were compared on spontaneous or glutamate-evoked discharge of globus pallidus (GP) neurons in rat. Our results demonstrate that mu and kappa opioid agonists are able to depress the excitability of pallidal neurons, possibly by interacting with mu and kappa opioid receptor subtypes, respectively. In addition, the mu agonists and dynorphin A-(1-13), but not the benzomorphans, enhanced the excitability of a number of pallidal neurons. We have proposed a presynaptic site as the basis for this opioid-induced excitation, possibly also mediated by a mu opioid receptor. The selectivity of dynorphin A-(1-13) for benzomorphan kappa opioid receptors in the rat GP appears to be low and dynorphin A-(1-13) may elicit effects that are different from those produced by the benzomorphan kappa agonists by virtue of its ability to interact with other opioid receptor subtypes, for example mu opioid receptors.
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PMID:Response of rat globus pallidus neurons to microintophoretically applied mu and kappa opioid receptor agonists. 257 94

Single-unit extracellular recording was carried out in rats to characterize the effects of dynorphin and several structurally related peptides on hippocampal pyramidal cell activity. Dynorphin, applied electrophoretically or by pneumatic pressure, produced a dose-dependent depression of both spontaneous and glutamate-evoked discharge in a majority (63%) of CA1 and CA3 cells tested. In addition, a small number of cells in both cellular fields responded to the peptide with a prolonged elevation in firing. The inhibitory effects of dynorphin were not blocked by naloxone. Moreover, administration of des-tyrosine-dynorphin depressed the firing of pyramidal cells in a manner similar to that of the parent compound. Ethylketocyclazocine produced a mixed pattern of excitatory and inhibitory effects, whereas naloxone-sensitive elevations in firing were most often observed with the application of dynorphin-(1-8). Application of [Leu5]enkephalin produced only facilitations in pyramidal cell firing. The possibility is raised that biologically significant non-opiate actions, in addition to potent opiate-mediated effects, may occur upon release of pro-dynorphin peptides in the hippocampus.
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PMID:Electrophysiological effects of dynorphin peptides on hippocampal pyramidal cells in rat. 285 95

Radiofrequency lesions of the anterior hypothalamic area reduced immunoreactive dynorphin (ir-DYN) in the hypothalamus and in the neurointermediate lobe of the pituitary. Ablation of the medial preoptic area was not associated with any significant modification of ir-DYN in the tissue examined. Destruction of the medial basal hypothalamus in parallel lowered ir-DYN in the hypothalamus and in both pituitary lobes. Neonatal administration of monosodium glutamate had no significant effect on ir-DYN. These findings indicate that changes of ir-DYN in the hypothalamus and pituitary are associated with the destruction of anatomically and functionally distinct neural systems.
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PMID:Effect of discrete brain lesions on hypothalamic and pituitary immunoreactive dynorphin. 287 29

In recent years, a number of new molecules, particularly peptides, have been identified as putative neurotransmitters. The basal ganglia, is especially rich in a number of classical transmitter molecules, amino acids and neuropeptides considered to function in neurotransmission. These include: the well-described terminal fields in the striatum which originate from the brain stem and contain the monoamines, dopamine and serotonin; amino acid containing axons projecting from the cortex and thalamus; striatal cholinergic and peptide-positive interneurons; and amino acid and peptide containing projection neurons to the globus pallidus and substantia nigra. Two amino acids, glutamate and aspartate, are considered to provide excitatory input to the striatum while gamma aminobutyric acid is thought to mediate inhibitory output. Neuropeptides which are richly concentrated in the basal ganglia include, enkephalin, dynorphin, substance P, somatostatin, neuropeptide Y and cholincystokinease. Changes in many of these peptide levels have recently been associated with a number of basal ganglia disorders.
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PMID:Neurotransmitters in the human and nonhuman primate basal ganglia. 287 74

While the dentate gyrus is clearly the simplest of the cortical fields that constitute the hippocampal formation, it nonetheless occupies a pivotal position in the flow of information through this region. Though it has been the subject of anatomical study for over a century and its major connections have been known for almost as long, the use of newly developed histochemical and immunohistochemical techniques have demonstrated many new facets of its intrinsic connectivity and afferent innervation. These techniques have established that it is innervated by cholinergic, noradrenergic, serotonergic and dopaminergic fibers. More recent studies have shown that fibers and cell bodies of the dentate gyrus are immunoreactive for variety of neuroactive substances including the excitatory amino acids glutamate and aspartate, the inhibitory transmitter GABA, as well as peptides of many types including the opioid peptides, enkephalin and dynorphin, several forms of somatostatin, neuropeptide Y, cholycystokinin, vasoactive intestinal peptide and substance P. In this review, we will briefly summarize the distribution of each of these putative transmitter systems within the dentate gyrus. The perspective emerges that the plethora of newly identified and chemically specific fiber systems enriches the classical understanding of the organization of this relatively simple cortical structure. Since there is thus far no evidence for the exclusion from the dentate gyrus of any class of transmitter bearing fiber or neuron found in the neocortex, it can be viewed as a relatively simple model system for studying the interactions of specific transmitter systems in a laminated, cortical structure.
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PMID:Transmitter systems in the primate dentate gyrus. 287 75

A procedure is described for the isolation of intact hippocampal mossy fiber synaptosomes. Electron microscopic examination revealed numerous synaptosomal profiles which are clearly of mossy fiber origin, indicated by their large size (2-6 micron diameter) and characteristic morphology. Furthermore, this fraction is enriched in zinc and dynorphin B which appear to be concentrated in mossy fiber terminals in vivo. Synaptosomes isolated by this procedure accumulated 2-deoxyglucose and retained 88% of total lactate dehydrogenase activity after incubation at 30 degrees C for 60 minutes, indicating a high degree of membrane integrity. Oxygen consumption was stimulated 4-fold by veratridine (0.1 mM) and inhibited 90% by ouabain (1 mM), suggesting that synaptosomal metabolism remained tightly coupled to ouabain-sensitive ATPase activity. Potassium-stimulated (45 mM) release of dynorphin B was completely dependent upon the presence of extrasynaptosomal calcium, while only 30% of the evoked release of glutamate was calcium-dependent. D-aspartate, which exchanges glutamate out of the cytoplasmic pool, virtually eliminated the calcium-independent component of glutamate release. This synaptosomal preparation will be useful in identifying the factors that modulate the release of amino acid and opioid neurotransmitters from hippocampal nerve terminals and in the investigation of their presynaptic mechanisms of action.
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PMID:Glutamate and dynorphin release from a subcellular fraction enriched in hippocampal mossy fiber synaptosomes. 290 27

Intracellular recordings were made from neocortical neurons in vitro. Application of D-Ala2-D-Leu5-enkephalin (DADL) by different methods produced a decrease in EPSP amplitude and in the amplitude of L-glutamate-induced depolarizations without changes in membrane potential or membrane input resistance. The DADL effects were blocked by naloxone and persisted when synaptic transmission was depressed, suggesting DADL acts on postsynaptically located opiate receptors. With dynorphin A (1-17), depolarizations, hyperpolarizations, decreases and increases in EPSP were observed, but never an anti-glutamate effect.
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PMID:Actions of D-Ala2-D-Leu5-enkephalin and dynorphin A (1-17) on neocortical neurons in vitro. 615 23

Dynorphin (1-13) and the mu-agonist, FK 33,824, have been applied microiontophoretically to single neurones in the hippocampus of the rat. Whereas FK 33,824 predominantly caused an increase in neuronal firing rates, dynorphin (1-13) decreased activity. Both effects were blocked by the opiate antagonist naloxone, whereas the effects induced by GABA and glutamate were not. This action of dynorphin (1-13) is comparable to that of other kappa-agonists in this brain region and suggests that dynorphin (1-13) may be a ligand for the kappa opiate receptor.
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PMID:Electrophysiological evidence for kappa-agonist activity of dynorphin in rat brain. 632 91

Parkinson's disease is characterized by an increased excitatory amino acid transmission in the internal segment of the globus pallidus and the substantia nigra pars reticulata. The effects of the kappa receptor agonist enadoline (CI-977) on glutamate transmission were investigated in vitro. Enadoline reduced the K(+)-evoked release of glutamate from slices of substantia nigra in a concentration-dependent manner (maximum effect: 78% inhibition at 200 microM). This effect was blocked by the selective kappa receptor antagonist nor-binaltorphimine. The endogenous ligand for kappa receptors is thought to be dynorphin. Dynorphin released from terminals of striato-pallidal and striato-nigral pathways might thus act as an endogenous modulatory agent on glutamatergic transmission in the basal ganglia. In vivo experiments were carried out in rodent and primate models of Parkinson's disease to assess the potential of manipulating kappa receptors as a potential treatment for Parkinson's disease. Enadoline reduced reserpine-induced akinesia when injected in the entopeduncular nucleus of the rat. Similarly, injections of CI-977 in the internal segment of globus pallidus (GPi) of the MPTP-treated marmoset alleviated parkinsonian symptoms and allowed the animal to recover its locomotor activity. This suggest that reducing the overactive glutamatergic transmission in the output regions of the basal ganglia by activating kappa receptors might potentially form the basis of a novel anti-parkinsonian therapy.
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PMID:Functional implications of kappa opioid receptor-mediated modulation of glutamate transmission in the output regions of the basal ganglia in rodent and primate models of Parkinson's disease. 755 34


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