Agonists and antagonists for excitatory amino acid receptors

Watkins, Johnathan; Olverman, Henry J.

doi:10.1016/0166-2236(87)90171-8

Cited by 566 publications

(194 citation statements)

References 30 publications

Supporting

Mentioning

185

Contrasting

Unclassified

Order By: Relevance

“…4), suggestive of noncompetitive antagonism. For com parison, the effect of D-APV, a known competitive antagonist (Watkins and Olverman, 1987), is also shown. In addition to their protective action against rap idly triggered, NMDA receptor-mediated injury, secobarbital and thiopental also attenuated the slowly triggered excitotoxicity induced by 24-h ex posure to 10 IJ-M a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) or 100 IJ-M kainate (Fig.…”

Section: Resultsmentioning

confidence: 99%

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Giffard

Weiss

Swanson

et al. 1993

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Summary:We examined the effects of secobarbital and other sedative-hypnotic barbiturates on the neuronal death induced by exposure to excitatory amino acids or deprivation of oxygen or glucose in mouse cortical cell cultures. N-Methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and kainate toxicities were attenuated in a concentration-dependent fashion by high concentrations of secobarbital or thiopen tal. Antagonism of NMDA toxicity was not overcome by increasing NMDA concentration and not mimicked by ,),-aminobutyrate. Despite these antiexcitotoxic actions, secobarbital exacerbated the neuronal death induced byBarbiturates are used clinically as sedatives, an esthetics, and anticonvulsants and have long been of interest as a method for reducing hypoxic ischemic brain injury. Twenty-five year ago, these drugs were found to prolong the survival of mice breathing 5% oxygen better than several other an esthetic agents (Wilhjelm and Arnfred, 1965). Sub sequently, high doses of barbiturates have been demonstrated to provide brain protection in several

show abstract

Section: Resultsmentioning

confidence: 99%

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Giffard

Weiss

Swanson

et al. 1993

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…In characterizing the glutamatergic transmitter system, the distinction between quisqualate/kainate (Q/K) and N-methyl-D-asparate (NMDA) receptors should be taken into account (CruneUi et al 1985;Watkins and Olverman 1987). While in many CNS regions Q/K receptors mediate the major part of EPSPs elicited by activation of glutamatergic fibers, the NMDA receptor subtype contributes only little to these EPSPs when the membrane potential of the postsynaptic neuron is close to resting level (Crunelli et al 1985;Herron et al 1986;Honor6 et al 1988).…”

Section: Introductionmentioning

confidence: 99%

Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro

et al. 1991

View full text Add to dashboard Cite

Summary. The principal aim of this study was to characterize the transmitter mechanisms mediating fast postsynaptic potentials in identified neurons of the rat nucleus accumbens. Using the biocytin-avidin labeling technique, impaled neurons were identified as medium spiny neurons. The basic membrane characteristics of these neurons were determined. Local electrical stimulation or stimulation of the corpus callosum elicited a depolarizing postsynaptic potential consisting of an EPSP often followed by an IPSP. The quisqualate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (4 gM) abolished most of the depolarizing postsynaptic potential. The N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid depressed a small part of the decay phase of the depolarizing postsynaptic potential. Paired-pulse facilitation of postsynaptic potentials was found using interstimulus-intervals between 10 and 150 ms. N-methyl-D-aspartate receptors were found to contribute only slightly to the facilitation of the decay phase of the depolarizing postsynaptic potential, but not to its rising phase. This contribution was particularly clear under conditions of reduced GABAA receptor mediated inhibition. The present study indicates that postsynaptic responses of medium spiny neurons in the nucleus accumbens to local stimulation or stimulation of neocortical afferents are primarily mediated by quisqualate/kainate receptors. The contribution of NMDA receptors is normally limited to a portion of the decay phase of these responses, but is enlarged in the absence of GABAergic inhibition and following paired-pulse stimulation.

show abstract

“…The most common classification of glutamate receptors is based on the relative efficacy of three agonists: N-methyl-D-aspartate (N-Me-DAsp), kainate, and quisqualate (1)(2)(3)(4). In chicken spinal cord neurons, kainate and quisqualate appear to compete for the same site, so we refer to only two' broad categories (2): G1 receptors are activated by N-Me-D-Asp and blocked by 2-amino-5-phosphonovalerate (APV) and Mg2 + (the latter in a voltage-dependent manner); G2 receptors are activated by kainate and quisqualate.…”

mentioning

confidence: 99%

Rapid desensitization of glutamate receptors in vertebrate central neurons.

Trussell¹,

Thio²,

Zorumski³

et al. 1988

Proceedings of the National Academy of Sciences

View full text Add to dashboard Cite

We have examined glutamate receptor desensitization in voltage-clamped embryonic chicken spinal cord neurons and postnatal rat hippocampal neurons maintained in culture. Rapid currents that rose in 0.8-3.6 msec were evoked when glutamate was ionophoresed with 0.5-to 1.0-msec pulses. With prolonged pulses or brief, repetitive pulses, glutamate-evoked currents decayed rapidly in a manner that was independent of holding potential. A similar desensitization occurred following close-range pressure ejection of glutamate. The rapid, desensitizing glutamate current exhibited a linear current-voltage relation and it was not blocked by 2-amino-5-phosphonovalerate, suggesting that it was mediated by N-methyl-D-aspartate-insensitive (G2) receptors. Desensitization of G2 receptors may be agonist-dependent: currents evoked by kainate, a selective G2 agonist, did not decay, whereas prior application of glutamate did reduce the size of kainate responses. The appearance of the rapid current depended critically on the position of the ionophoretic pipette. Such glutamate-receptor "hot spots" often corresponded to points of contact with neighboring neurites, which raises the possibility that they are located at synapses.Glutamate is considered to be a "mixed agonist" in that it activates more than one type of receptor. The most common classification of glutamate receptors is based on the relative efficacy of three agonists: N-methyl-D-aspartate (N-Me-DAsp), kainate, and quisqualate (1-4). In chicken spinal cord neurons, kainate and quisqualate appear to compete for the same site, so we refer to only two' broad categories (2): G1 receptors are activated by N-Me-D-Asp and blocked by 2-amino-5-phosphonovalerate (APV) and Mg2 + (the latter in a voltage-dependent manner); G2 receptors are activated by kainate and quisqualate. In addition, G1, but not G2, currents are desensitized following prolonged or repeated application of glutamate (or more selective agonists) over a period of several seconds (5).It is important to determine whether receptor desensitization occurs on the time scale of synaptic transmission. Our previous studies did not address this issue because the agonists were applied by pressure ejection from pipettes located 25-50 ,um away from the target neuron (2,5,6). In this situation, the buildup of agonist concentration at the receptor sites is slow compared to the time course of synaptically released transmitter. In addition, such a diffuse application must activate extrasynaptic as well as synaptic receptors.In this study, we examined rapid desensitization following focal ionophoresis or close-range pressure ejection of glutamate and other agonists. Responses evoked at extremely sensitive sites (hot spots) on the neuronal surface were desensitized rapidly. The desensitizing currents were not blocked by APV. These data suggest that G2 receptors are, in fact, desensitized but with a time course that is >2 orders of magnitude faster than G1 receptor desensitization. Some of these results have been presented in abst...

show abstract

Agonists and antagonists for excitatory amino acid receptors

Cited by 566 publications

References 30 publications

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro

Rapid desensitization of glutamate receptors in vertebrate central neurons.

Contact Info

Product

Resources

About