Structure--activity relationships of L-glutamate receptor ligands: role of the omega-acidic terminal.
Acidic amino acid analogues varying in their omega-terminal were evaluated: (1) as neuronal excitants or antagonists of excitatory synaptic transmission, and (2) as inhibitors of L-[3H]glutamate binding to synaptic membranes. omega-Phosphonates were antagonists and inhibited L-glutamate binding to the 2-amino-4-phosphonobutyrate (APB)-sensitive population of binding sites; omega-sulfonates and omega-carboxylates were excitants and inhibited L-glutamate binding to APB-sensitive and -insensitive sites. The data indicate that properties of the omega-acidic group are important for establishing the relative potencies of antagonist substances and the overall excitatory/antagonist activity of these analogues.
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D010768:Phosphoserine / Q000494:pharmacology; D010769:Phosphothreonine / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000613:Aminobutyrates; D005971:Glutamates; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; D010769:Phosphothreonine; D010768:Phosphoserine; D018698:Glutamic Acid; C012729:2-amino-4-phosphonobutyric acid