The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. 1983

G L Collingridge, and S J Kehl, and H McLennan

1. The effects of the ionophoretic application of a number of excitatory amino acids and antagonists to the dendrites of CA1 neurones of rat hippocampal slices maintained in vitro were examined. Cells were excited by N-methyl-DL-aspartate (NMA), kainate, quisqualate, L-aspartate and L-glutamate; NMA was unique in causing cells to fire in bursts of repetitive discharges in contrast to the sustained firing seen with the other compounds. 2. D-(-)-alpha-aminoadipate (DAA) and (+/-)-2-amino-5-phosphonovalerate (APV) were selective NMA antagonists, the latter appearing to be the more potent; in addition both compounds potentiated the responses to kainate and quisqualate. L-glutamate excitations were affected less by APV than were those of L-aspartate. The antagonist properties of APV appeared to reside with the D-(-)-isomer. 3. gamma-D-glutamylglycine (DGG) in low ionophoretic doses inhibited NMA-, kainate- and aspartate-induced cell firing but at higher doses the quisqualate and glutamate responses were also decreased. 4. Kainate and NMA responses were blocked by D-(-)-2-amino-4-phosphonobutyrate (D-APB) which also had some action against the excitatory effects of L-aspartate. L-APB had no antagonistic effects, but often produced potentiation of amino acid excitations or was itself an excitant. 5. The effects of NMA and those of kainate and quisqualate were blocked by (+/-)-cis-2,3-piperidine dicarboxylate (PDA), but this compound itself had a direct excitatory effect. L-glutamate diethylester (GDEE) did not show specific antagonism of any amino acid excitations. 6. DGG and APV did not affect ACh excitations and these selective antagonists should be of value in studying the involvement of the excitatory amino acids in synaptic transmission in the hippocampus. Because they are less potent and/or have complicating direct effects PDA, GDEE, D- and L-APB may be less useful in this regard.

UI MeSH Term Description Entries
D007608 Kainic Acid (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010069 Oxadiazoles Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms. Oxadiazole
D004151 Dipeptides Peptides composed of two amino acid units. Dipeptide
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001224 Aspartic Acid One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. (+-)-Aspartic Acid,(R,S)-Aspartic Acid,Ammonium Aspartate,Aspartate,Aspartate Magnesium Hydrochloride,Aspartic Acid, Ammonium Salt,Aspartic Acid, Calcium Salt,Aspartic Acid, Dipotassium Salt,Aspartic Acid, Disodium Salt,Aspartic Acid, Hydrobromide,Aspartic Acid, Hydrochloride,Aspartic Acid, Magnesium (1:1) Salt, Hydrochloride, Trihydrate,Aspartic Acid, Magnesium (2:1) Salt,Aspartic Acid, Magnesium-Potassium (2:1:2) Salt,Aspartic Acid, Monopotassium Salt,Aspartic Acid, Monosodium Salt,Aspartic Acid, Potassium Salt,Aspartic Acid, Sodium Salt,Calcium Aspartate,Dipotassium Aspartate,Disodium Aspartate,L-Aspartate,L-Aspartic Acid,Magnesiocard,Magnesium Aspartate,Mg-5-Longoral,Monopotassium Aspartate,Monosodium Aspartate,Potassium Aspartate,Sodium Aspartate,Aspartate, Ammonium,Aspartate, Calcium,Aspartate, Dipotassium,Aspartate, Disodium,Aspartate, Magnesium,Aspartate, Monopotassium,Aspartate, Monosodium,Aspartate, Potassium,Aspartate, Sodium,L Aspartate,L Aspartic Acid

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