Monosodium glutamate: increased neurotoxicity after removal of neuronal re-uptake sites

Microinjections of monosodium glutamate (MSG; 300 μg/0.5 μl) into the hippocampus of the adult rat result in only marginal damage to local neurons. Perforant path transections, removing glutamatergic afferents to hippocampal granule cells, make the latter markedly more vulnerable to a subsequent MSG injection. The principle of modulating toxic effects of MSG by interfering with its neurotransmitter role may have significant impact on our understanding of human neurodegenerative disorders.     

Cations differentially affect subpopulations ofl-glutamate receptors in rat synaptic plasma membranes

Several cations were examined for their ability to specifically affect one of the 3l-glutamate (l-Glu) binding sites in rat forebrain synaptic plasma membranes (i.e. Na⁺-dependent, Cl⁻-dependent and Cl⁻-independent). Na⁺-dependent binding was potently inhibited by K⁺ and NH₄⁺ ions. Other monovalent cations testedd (Cs⁺, Li⁺, triethylammonium) had no effect on this binding site. Polyvalent cations (Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺ and Cr³⁺) also had little effect on the Na⁺-dependentl-Glu binding site. Cl⁻-dependentl-Glu binding was potently inhibited by Na⁺ ions but was not affected by other monovalent ions. All of the divalent cations were potent inhibitors of both Cl⁻-dependent and -independent binding. The results show that these binding sites ofl-Glu can be distinguished by their response to cations and suggest possible novel modes of regulation in vivo.     

Effects of anticonvulsants and other agents on seizures induced by intracerebral l-glutamate

Convulsions induced in mice by intracerebral injection of l-glutamate were antagonized by phenytoin, phenobarbital, chlordiazepoxide and valproic acid. Trimethadione had only a small effect at the dose used, and ethosuximide was ineffective. The profile of interaction of glutamate with these antiepileptic agents resembles that of ouabain, and differs considerably from the profiles of other convulsants previously tested. However, muscimol had a small potentiating effect on glutamate but not on ouabain. Neither l-glutamic acid diethyl ester nor l-nuciferine significantly altered the convulsive response to glutamate.     

Pharmacological differentiation between responses of rat medullary dorsal horn neurons to noxious mechanical and noxious thermal cutaneous stimuli

Responses of lamina V medullary dorsal horn neurons to noxious thermal and noxious mechanical facial stimuli were challenged with iontophoretically appliedcis-2,3-piperidine dicarboxlic acid, a broad spectrum excitatory amino acid antagonist. This antagonist reduced neuronal responses to noxious mechanical stimuli but not responses to noxious thermal stimuli. These results suggest that different neural mechanisms underlie the responses of lamina V neurons to different noxious stimuli, and that responses to noxious mechanical stimuli appear to involve excitatory amino acid receptors.     

Ultrastructural demonstration ofl-glutamate decarboxylase and cysteinesulfinic acid decarboxylase in rat retina by immunocytochemistry

The γ-aminobutyric acid (GABA) synthesizing enzyme,l-glutamate decarboxylase (GAD), and the taurine synthesizing enzyme, cysteinesulfinic acid decarboxylase (CSAD) have been localized in rat retina at the ultrastructural level by indirect immunoelectron microscopy. GAD immunoreactivity (GAD-IR) was seen only in some amacrine cells and their terminals. CSAD immunoreactivity (CSAD-IR) was found in most retinal neuronal types and their processes including photoreceptor cells (rod and cone cells), bipolar cells, amacrine cells and ganglion cells. The GAD-IR positive amacrine terminals have been found to make synaptic contact with other GAD-IR negative bipolar and amacrine terminals, and ganglion cell dendrites. Most of the GAD-IR positive terminals are presynaptic. Occasionally, GAD-IR positive amacrine terminals are postsynaptic to another amacrine terminal or ganglion cell body. In the inner plexiform layer, CSAD-IR positive amacrine terminals also make synaptic contacts with other nerve terminals, similar to that of GAD-IR positive amacrine terminals. In addition, CSAD-IR positive bipolar terminals make synaptic contact with some CSAD-IR positive as well as negative amacrine terminals. Both CSAD-IR positive amacrine and bipolar terminals are mostly presynaptic to other CSAD-IR negative terminals. In the outer plexiform layer, CSAD-IR was found to be associated with synaptic vesicles and the synaptic membrane in certain cone pedicles and rod spherules. It is concluded that only a fraction of amacrine cells in rat retina may use GABA as a neurotransmitter. The presence of CSAD-IR in some amacrine, bipolar, photoreceptor and ganglion cells in rat retina is compatible with the notion that taurine may play some important roles, such as those of neurotransmitter or neuromodulator in mammalian retina.     

L-glutamate activates RhoA GTPase leading to suppression of astrocyte stellation

The actin cytoskeleton is known to support cellular morphological changes. Rho family small GTPases function as switching molecules to promote the convergence of both extracellular and intracellular signals in regulating cytoskeletal organization. Evidence indicates that L-glutamate suppresses morphological changes of astrocytes over a broad spectrum. To test the possibility that L-glutamate affects cytoskeletal reorganization, we investigated its effect on morphological changes induced by manganese exposure. L-glutamate concentration-dependently prevented and reversed manganese-induced astrocyte stellation and cytoskeletal disruption. The suppressive effect of L-glutamate on manganese-induced stellation was mediated by the activation of the glutamate transporter rather than ionotropic or metabotropic glutamate receptors. Pharmacological and biochemical approaches revealed the involvement of Ras homolog gene family, member A (RhoA) activation in L-glutamate-mediated suppression of manganese-induced stellation. The activation of RhoA by L-glutamate was partly through the up-regulation of guanine nucleotide exchange factor phosphorylation and was abrogated by competitive nonsubstrate inhibitors. Furthermore, the hyperphosphorylation of myosin light chain and cofilin through the activation of RhoA following L-glutamate treatment synergistically stabilized actin stress fibres. These results suggest that manganese-induced stellation is suppressed by a mechanism involving glutamate transporters. Our in vitro findings also strongly indicate that astrocyte morphological plasticity is under the control of RhoA and that manganese and L-glutamate regulate astrocyte morphology by modulating this switching molecule under culture conditions.     

l-Glutamate depolarizes ON-OFF transient type of amacrine cells in the carp retina: an ionophoretic study

Amacrine cells generating the ON-OFF transient type of photoresponse, which is most frequently encountered, were identified by intracellular recording and staining with a fluorescent dye Lucifer Yellow in the carp (Cyprinus carpio) retina.l-Glutamate applied ionophoretically slowly depolarized the amacrine cells by about 10 mV and reduced their photoresponses during the application. Such changes gradually recovered following the cessation ofl-glutamate injection. The results indicate that this amino acid directly activates the ON-OFF type amacrine cells.     

Receptor types mediating the excitatory actions of exogenousl-aspartate andl-glutamate in rat olfactory cortex

Changes in potential between the pial and cut surfaces of rat olfactory cortex slices evoked by N-methyl-d-aspartate (NMDA), quisqualate, kainate,l-glutamate andl-aspartate and also by γ-aminobutyric acid (GABA) have been monitored using extracellular electrodes. All agonists produced a pial-negative potential response when superfused onto the pial surface, GABA,l-aspartate andl-glutamate being less potent than the others. Repeated applications of NMDA, but not of the other agonists, led to a progressive reduction in response to approximately 30% of the initial depolarization. The responses to NMDA (100 μM) were selectively abolished by(±)2-amino-5-phosphonopentanoic acid (APP; 100 μM) while depolarizations evoked byl-glutamate andl-aspartate (both at 10 mM) were only antagonized by21 ± 2 (n = 12) and36 ± 3 (n = 12) percent respectively (means ± S.E.M.). γ-d-Glutamylglycine (γ-DGG; 1 mM) and(±)cis-2,3-piperidine dicarboxylate (cis-PDA; 2 and 5 mM), in addition to antagonizing responses to NMDA, also partially blocked quisqualate- and kainate-evoked depolarizations. When a mixture of APP (100 μM), γ-DGG (1 mM) and cis-PDA (5 mM) was applied to preparations, although NMDA receptors were completely blocked and responses to both quisqualate and kainate antagonized by approximately 80%,l-glutamate andl-aspartate evoked depolarizations were only reduced by51 ± 7 (n = 4) and 49 ± 4 (n = 4) percent respectively (means ± S.E.M.). The results are discussed in terms of the contributions made by NMDA, quisqualate and kainate receptors to the composite responses evoked byl-aspartate andl-glutamate.     

Response properties of the pharyngeal branch of the glossopharyngeal nerve for umami taste in mice and rats

Many studies have reported the mechanism underlying umami taste. However, there are no investigations of responses to umami stimuli taste originating from chemoreceptors in the pharyngeal region. The pharyngeal branch of the glossopharyngeal nerve (GPN-ph) innervating the pharynx has unique responses to taste stimulation that differs from responses of the chorda tympani nerve and lingual branch of the glossopharyngeal nerve. Water evokes robust response, but NaCl solutions at physiological concentrations do not elicit responses. The present study was designed to examine umami taste (chemosensory) responses in the GPN-ph. Response characteristics to umami taste were compared between mice and rats. In mice, stimulation with compounds eliciting umami taste (0.1 M monosodium l-glutamate (MSG), 0.01 M inosine monophosphate (IMP) and the mixture of 0.1 M MSG + 0.01 M IMP) evoked higher responses than application of distilled water (DW). However, synergistic response of a mixture of 0.1 M MSG + 0.01 M IMP was not observed. In rats, there is no significant difference between the responses to umami taste (0.1 M MSG, 0.01 M IMP and the mixture of 0.1 M MSG + 0.01 M IMP) and DW. Monopotassium glutamate (MPG) was used in rats to examine the contribution of the sodium component of MSG on the response. Stimulation with 0.1 M MPG evoked a higher response when compared with responses to DW. The present results suggest that umami taste compounds are effective stimuli of the chemoreceptors in the pharynx of both mice and rats.