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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 effect of caudate nucleus (CN)-injections of the glutamate agonist DL-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), viz. an agonist of quisqualate receptors, on switching behaviour was investigated: first, cats had to switch from hanging with the forepaws on the bar to climbing on the bar; then, they had to switch to walking; finally, they had to switch to jumping off the bar. AMPA induced limb deficits, i.e. unilateral incorrect or absent placing of the fore- and/or hindlimb, in part of the tested cats; in the remainder of the tested animals AMPA reduced climbing time. Limb deficits were prevented by the broad-spectrum glutamate antagonist kynurenic acid (KYN) and by the selective NMDA antagonist D-2-amino-7-phosphono-heptanoate. In all cats AMPA increased the number of head movements as well as that of walking-restarts. These effects were counteracted only by KYN. These data show that part of the AMPA-induced effects were selectively mediated by quisqualate receptors. The present data are discussed in view of the role of the caudate nucleus in switching behaviour.
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PMID:Enhancement in switching motor patterns following local application of the glutamate agonist AMPA into the cat caudate nucleus. 216 Feb 48

Bilateral intracaudate application of the glutamate agonist DL-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), viz. an agonist of quisqualate receptors, is known to produce the following effects in cats that had to climb on a small wooden bar and, subsequently, to switch to distinct patterns: it produces increases in switching from one pattern to another pattern (1) and it induces limb deficits, i.e. unilateral deficient placing of the fore- and/or hindlimb. In the present study, the effect of stimulating striatal dopamine receptors on behavioural changes induced by intracaudate injections of AMPA was investigated. Therefore, the dopamine agonist apomorphine was injected into the caudate nucleus 5 min before the striatal injection of 1.0 micrograms AMPA. AMPA-induced increases in switching behaviour were prevented by 0.6 micrograms, but not 0.3 micrograms, apomorphine. In contrast, AMPA-induced limb deficits were not prevented by pretreatment of apomorphine. In view of the notion that the dopaminergic caudate nucleus, its output station the substantia nigra, pars reticulata and the nigral output station the deeper layers of the colliculus superior are essential for switching behaviour, but not for the display of disturbances like AMPA-induced limb deficits, the present data strongly suggest that only AMPA-induced changes in switching, but not AMPA-induced limb deficits, are mediated by the caudato-nigro-collicular circuitry. The glutamate receptor-selectivity of the modulatory action of dopamine is discussed.
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PMID:Effects of intrastriatal apomorphine on changes in switching behaviour induced by the glutamate agonist AMPA injected into the cat caudate nucleus. 216 Feb 49

Four cloned cDNAs encoding 900-amino acid putative glutamate receptors with approximately 70 percent sequence identity were isolated from a rat brain cDNA library. In situ hybridization revealed differential expression patterns of the cognate mRNAs throughout the brain. Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX).
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PMID:A family of AMPA-selective glutamate receptors. 216 37

The effects of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), 4-chloro-2-methylphenoxyacetic acid (MCPA) and 2-(2,4,5-trichlorophenoxy)propionic acid (2,4,5-TP) on respiration and oxidative phosphorylation in rat liver mitochondria were examined in vitro. Respiration rates of glutamate, malate and succinate were investigated in the presence of each herbicide (0.1-4.0 mM). At lower concentrations, all herbicides stimulated state 4 respiration, decreased the respiratory control ratio and the ADP/O ratio. The respiration rate in state 3 and uncoupled state was unaffected. At higher concentrations all bioenergetic parameters, respiration in state 4, 3 and uncoupled state, as well as respiratory control ratio and ADP/O, were inhibited in a concentration-dependent manner. These data indicate that these herbicides alter energy metabolism in rat liver mitochondria by uncoupling of oxidative phosphorylation. 2,4,5-TP possesses the strongest uncoupling properties followed by 2,4,5-T, MCPA and 2,4-D in that order.
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PMID:Comparison of uncoupling activities of chlorophenoxy herbicides in rat liver mitochondria. 235 68

The actions of the putative quisqualate-selective agonist DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) were examined in identified embryonic chick motoneurons using gigaseal recording techniques and compared with properties of the selective non-NMDA excitatory amino acid agonists kainate and quisqualate. Pressure application of AMPA induces an inward going current when neurons are voltage-clamped at negative membrane potentials. The current-voltage relationship for this response is linear with reversal near 0 mV. Over the range of 1 microM-10 mM, the AMPA-induced current is dose-dependent with an ED50 of 40 microM. AMPA currents are insensitive to the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate, and the putative quisqualate selective blocker, glutamate diethyl ester, but are partially inhibited by kynurenic acid. In competition experiments, applications of saturating concentrations of AMPA and either kainate or quisqualate produce responses intermediate between the response to either agonist alone, indicating commonality in the mechanism of these agents. Applications of AMPA with the NMDA-selective agonist aspartate give an additive response. Analysis of current fluctuations indicates that AMPA, quisqualate, and kainate gate a channel with a primary conductance near 20 pS. Differences in maximal macroscopic current evoked by saturating concentrations of AMPA, kainate, and quisqualate cannot be explained by differences in mean channel open time as the most efficacious agonist, kainate, has the shortest channel open time (AMPA = 5.9 +/- 0.4 msec, kainate = 2.7 +/- 0.1 msec, quisqualate = 5.0 +/- 0.5 msec). Rather, kainate induces a greater frequency of channel opening. This finding contrasts with results obtained at the nicotinic ACh receptor, where the most efficacious agonists have the longest mean channel open time. Our results suggest that AMPA acts at the same receptor-channel complex as kainate and quisqualate on chick motoneurons and support the hypothesis that only 2 classes of excitatory amino acid receptor complexes exist in this preparation.
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PMID:AMPA, kainate, and quisqualate activate a common receptor-channel complex on embryonic chick motoneurons. 246 May 95

1. Inward going membrane currents elicited by N-methyl-D-aspartate (NMDA), glutamate (GLU), and glutamate analogues were recorded from isolated catfish (Ictalurus punctatus) cone horizontal cells using the patch-clamp technique in the whole-cell mode. 2. Currents elicited by the N-methyl-D-aspartate receptor agonists NMDA, L-aspartate (ASP) or L-homocysteate (L-HCA) in nominally Mg-free saline were completely blocked by 100 microM 2-amino-5-phosphonovalerate (AP-5) but responses to non-NMDA receptor agonists kainate (KA), quisqualate (QA), or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) in normal Mg2+ saline were unaffected. Responses to GLU were partially blocked. Kynurenic acid (1 mM) effectively blocked responses to all agonists. 3. Concentration-response curves obtained from measured responses in the presence of different NMDA receptor agonists gave Hill coefficients of near 1 indicating a single binding site for channel activation. The rank order of agonist affinity at the NMDA receptor is L-HCA greater than NMDA greater than ASP. Glycine potentiates responses to NMDA in horizontal cells. 4. The NMDA-activated channel is blocked in a voltage-dependent manner by Mg2+, Ni2+, and Co2+ and in a voltage-independent manner by Zn2+. Both the NMDA- and KA-activated channel were permeable to monovalent cations but the NMDA-activated channel appeared to have a greater permeability to Ca2+ than the KA-activated channel. 5. Concentration-response curves measured from responses to the non-NMDA receptor agonists QA, KA, and AMPA gave Hill coefficients of approximately 1.5 suggesting multiple binding sites for channel activation and cooperativity. The rank-order affinity was QA greater than AMPA greater than GLU greater than KA. KA was the most efficacious of the agonists resulting in the largest Imax. Rapid desensitization was observed only in the presence of QA, AMPA, or GLU and this desensitization could be removed by pretreatment with conconavalin A (Con A). 6. Single-channel conductance and mean open time were measured from the fluctuations in current noise in the presence of the agonists. The single-channel conductance estimated from the slope of a linear regression obtained from a plot of the variance of the conductance versus the whole-cell conductance measured in NMDA and ASP was 4.7 pS. The mean channel open time was 1.3 ms. These same parameters measured for KA and QA were 5.7 and 5.9 pS and 1.1 to 1.3 ms, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Horizontal cells isolated from catfish retina contain two types of excitatory amino acid receptors. 247 74

Cultured astrocytes from neonatal rat cerebral hemispheres are depolarized by the excitatory neurotransmitter glutamate. In this study we have used selective agonists of different neuronal glutamate receptor subtypes, namely, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate type, to characterize pharmacologically the glutamate receptor in astrocytes. The agonists of the neuronal quisqualate receptor, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) and quisqualate, depolarized the membrane. Kainate, an agonist of the neuronal kainate receptor, depolarized astrocytes more effectively than quisqualate. Combined application of kainate and quisqualate depolarized astrocytes to a level which was intermediate to that evoked by quisqualate and kainate individually. Agonists activating the neuronal NMDA receptor, namely NMDA and quinolinate, were ineffective. Application of NMDA did not alter the membrane potential even in combination with glycine or in Mg2+-free solution, conditions under which neuronal NMDA receptor activation is facilitated. The nonselective agonists L-cysteate, L-homocysteate, and beta-N-oxalylamino-L-alanine (BOAA) mimicked the effect of glutamate. Dihydrokainate, a blocker of glutamate uptake, did not, and several antagonists of neuronal glutamate receptors only slightly affect the glutamate response. These findings suggest that astrocytes express one type of glutamate receptor which is activated by both kainate and quisqualate, lending further support to the notion that cultured astrocytes express excitatory amino acid receptors which have some pharmacological similarities to their neuronal counterparts.
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PMID:Pharmacological characterization of the glutamate receptor in cultured astrocytes. 254 Mar 40

Calcium-activated potassium conductances play important roles in modulating neuronal excitability. Indeed, the effects of some neurotransmitters such as acetylcholine and norepinephrine are, in part, due to actions on these conductances. We have found that the N-methyl-D-aspartate (NMDA) class of excitatory amino acid receptors also is coupled to a calcium activated potassium current. In voltage-clamped postnatal rat hippocampal neurons, NMDA responses consist of an initial inward cationic current followed by a slowly developing outward current carried by potassium ions. The slow outward current always follows the inward current, is associated with an increase in membrane conductance and is dependent on the influx of calcium ions. Similar responses are produced by other agonists active at NMDA receptors, including aspartate, glutamate and ibotenate, but are not activated by kainate, quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA). Inhibition of the NMDA gated inward current by a competitive antagonist, 2-amino-5-phosphonovalerate (APV), eliminates the outward current. From these results we conclude that calcium influx through NMDA channels activates a potassium current. The extended time course of this outward current suggests that NMDA receptors may modulate neuronal excitability long after the opening of the NMDA channel.
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PMID:Calcium influx through N-methyl-D-aspartate channels activates a potassium current in postnatal rat hippocampal neurons. 254 45

We report here the characterization of the arginine binding site(s) and corroborative neurophysiological studies. Binding of L-[3H]arginine to Fraction P2 from taste epithelium was measured by a modification of the method of Krueger and Cagan. Parameters for measuring maximal binding activity were established for both duration of incubation and pH of medium. At pH 7.8, the apparent single rate constant for association (kobs) at 4 degrees C was 4.72 x 10(+5).M-1.min-1. Dissociation was more complex, yielding two rate constants of 1.77.min-1 and 8.34 x 10(-3).min-1. These data suggest the presence of two affinity states for L-arginine. The KD values as calculated from the ratio k-1/k+1 were 1.3 x 10(-6) M and 1.8 x 10(-8) M. Homologous inhibition studies of L-arginine binding were not fit by a simple mass action relationship (Hill Coefficient 0.79), but were best fit by a two-site model with IC50 values of 1.6 x 10(-6) M for the high affinity state and 9 x 10(-4) M for the low affinity state. Multiunit neural recordings examined the stimulatory effectiveness of a number of guanidinium-containing compounds. Compared with L-arginine, only L-arginine methyl ester and L-alpha-amino-beta-guanidino propionic acid (L-AGPA) were effective stimuli. Cross-adaptation experiments demonstrated that at 10(-4) M L-arginine methyl ester, L-AGPA and, to a lesser extent, D-arginine were effective cross-adapting stimuli to 10(-6) M L-arginine. In competition binding studies L-arginine methyl ester, L-AGPA and D-arginine also inhibited binding of L-[3H]arginine (10(-6) M), but each recognized only one affinity state. Inhibition by the poorly cross-adapting stimuli L-glutamate, glycine and L-alanine occurred only above 10(-3) M, indicating that the binding sites for L-arginine are selective. These studies suggest that there are at least two affinity states of L-arginine binding, that the binding sites are specific, and that effective agonists of L-arginine receptors must contain a guanidinium group and an unblocked L-alpha-amino group.
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PMID:Specific L-arginine taste receptor sites in the catfish, Ictalurus punctatus: biochemical and neurophysiological characterization. 254 99

beta-N-Oxalylamino-L-alanine (L-BOAA) is a non-protein excitatory amino acid present in the seed of Lathyrus sativus L. This excitotoxin has been characterized as the causative agent of human neurolathyrism, an upper motor neuron disease producing corticospinal dysfunction from excessive consumption of the lathyrus pea. Previous behavioral, tissue-culture, and in vitro receptor binding investigations revealed that L-BOAA might mediate acute neurotoxicity through quisqualate (QA)-preferring glutamate receptors. The present study demonstrates the stereospecific action of L-BOAA on glutamate receptor binding in whole mouse brain synaptic membranes. L-BOAA was most active in displacing thiocyanate (KSCN)-sensitive specific tritiated (RS)-alpha-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding (i.e., QA receptor) (Ki = 0.76 microM) with a rank-order potency of QA greater than kainate greater than N-methyl-D-aspartate (NMDA). By contrast, the nonneurotoxic D-BOAA isomer (100 microM) was essentially inactive in displacing radioligands for glutamate receptors, except the NMDA site, where it was equipotent with L-BOAA. Scatchard analysis of L-BOAA displacement of specific [3H]AMPA binding indicated competitive antagonism (KD: control, 135 nM; L-BOAA, 265 nM) without a significant change in QA-receptor density, and Hill plots yielded coefficients approaching unity. Differential L-BOAA concentration-dependent decreases in specific [3H]AMPA binding were observed in synaptic membranes, indicating that the neurotoxin was more potent in displacing specific binding from frontal cortex membranes, followed by that for corpus striatum, hippocampus, cerebellum, and spinal cord. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-N-oxalylamino-L-alanine action on glutamate receptors. 254 98


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