title: Pharmacological properties of the N-methyl-D-aspartate receptor system coupled to the evoked release of gamma-[3H] aminobutyric acid from striatal neurons in primary culture.
abstract: The actions of a series of endogenous excitatory amino acid (EAA) agonists and synthetic antagonists at the N-methyl-D-aspartate (NMDA) receptor system coupled to the evoked release of gamma-[3H]aminobutyric acid (GABA) from purified populations of striatal neurons in primary culture were examined. EAA agonists displayed the following rank order of potency in evoking [3H]GABA release: glutamate greater than homocysteate greater than aspartate, NMDA greater than cysteine sulfinate. Glutamate, homocysteate and cysteine sulfinate were equieffective, whereas at saturating concentrations, aspartate and NMDA reached 75 and 65%, respectively, of the maximum efficacy of the former three agonists. The release of [3H]GABA evoked by 100 microM NMDA was attenuated in a dose-dependent manner by the following antagonists (IC50, micromolar): MK-801 (0.067), phencyclidine (0.151), CGS-19755 (3.31), 2-aminophosphonovalerate (18.8), kynurenate (100) and gamma-D-glutamylglycine (100). The antagonist properties of MK-801 and phencyclidine were not competitive with NMDA, whereas NMDA dose-response curves performed in the absence and presence of increasing concentrations of CGS-19755 resulted in parallel rightward shifts (pA2 = 5.95). CGS-19755 produced similar rightward shifts of the homocysteate dose-response curve (pA2 = 5.89). At glutamate concentrations less than 100 microM, CGS-19755 and 2-aminophosphonovalerate were potent antagonists of glutamate-evoked release; however, at glutamate concentrations greater than 100 microM these agents were ineffective blockers. The blockade of NMDA-evoked release of [3H]GABA by kynurenate was not competitive in nature.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pathology, University of Calgary Faculty of Medicine, Alberta, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Weiss
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010875:Pipecolic Acids; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D005971:Glutamates; D010875:Pipecolic Acids; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; C053672:selfotel; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D005998:Glycine