Utilization of the resolvedl-isomer of 2-amino-6-phosphonohexanoic acid (l-AP6) as a selective agonist for a quisqualate-sensitized site in hippocampal CA1 pyramidal neurons
| Autor: | David J. Chalmers, Marvin K. Schulte, Robert J. Roon, James F. Koerner, David C. Sunter |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Agonist medicine.drug_class Stereochemistry Kainate receptor AMPA receptor In Vitro Techniques Biology Hippocampus Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley chemistry.chemical_compound Neural Pathways Norleucine medicine Animals Quisqualic acid Receptors AMPA Receptor Evoked Potentials Molecular Biology chemistry.chemical_classification Pyramidal Cells General Neuroscience Glutamate receptor Quisqualic Acid Stereoisomerism Rats Amino acid 2-Amino-5-phosphonovalerate Biochemistry chemistry NMDA receptor sense organs Neurology (clinical) Extracellular Space Developmental Biology |
| Zdroj: | Brain Research. 649:203-207 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/0006-8993(94)91065-0 |
| Popis: | Brief exposure of rat hippocampal slices to quisqualic acid (QUIS) sensitizes neurons to depolarization by the α-amino-ω-phosphonate excitatory amino acid (EAA) analogues AP4, AP5 and AP6. These phosphonates interact with a novel QUIS-sensitized site. Whereas l -AP4 and d -AP5 cross-react with other EAA receptors, dl -AP6 has been shown to be relatively selective for the QUIS-sensitized site. This specificity of dl -AP6, in conjuction with the apparent preference of this site for l -isomers, suggested that the hitherto unavailable l -isomer of AP6 would be a potent and specific agonist. We report the resolution of the d - and l -enantiomers of AP6 by fractional crystallization of the l -lysine salt of dl -AP6. We also report the pharmacological responses of kainate / AMPA, NMDA, lateral perforant path l -AP4 receptors and the CA1 QUIS-sensitized site to d - and l -AP6, and compare these responses to the d - and l -isomers of AP3, AP4, AP5 and AP7. The d -isomers of AP4, AP5 and AP6 were 5-, 3- and 14-fold less potent for the QUIS-sensitized site than their respective l -isomers. While l -AP4 and l -AP5 cross-reacted with NMDA and l -AP4 receptors, l -AP6 was found to be highly potent and specific for the QUIS-sensitized site (IC50 = 40 μM). Its IC50 values for kainate / AMPA, NMDA and l -AP4 receptors were > 10, 3 and 0.8 mM, respectively. As with AP4 and AP5, sensitization to l -AP6 was reversed by l -α-aminoadipate. |
| Databáze: | OpenAIRE |
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