Structure - function relationships for gamma-substituted glutamate analogues on dentate granule cells.
We previously demonstrated in the Schaffer collateral-CA1 region of the hippocampus that bath-applied agonists could be distinguished from antagonists among a group of acidic amino acid analogues by extracellular recording techniques. Here we report the use of the extracellular signs of agonist activity for discerning agonists and antagonists among several gamma-substituted glutamate analogues tested in the perforant path. The two-pathway composition of the perforant path offers the advantage over CA1 in that pathway-specificity, a postulated characteristic of antagonists, may be tested. By extracellular recording, D- and L-homocysteic acid, L-serine-O-sulfate, and L-2-amino-4-(5-tetrazolyl)-butanoic acid [L-glutamate tetrazole] were identified as agonists, and all 4 analogues were more potent than L-glutamate for inhibiting synaptic field potentials. Two previously identified antagonists, L-2-amino-4-phosphonobutyric acid and L-O-phosphoserine, exhibited the pathway-specificity and inhibitory kinetics consistent with properties expected for antagonists; both compounds detected 3 perforant path components with the same rank in sensitivity, suggesting that they are acting on the same set of receptors.
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005971:Glutamates / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D010768:Phosphoserine / Q000494:pharmacology; D051381:Rats; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology
D000613:Aminobutyrates; D005971:Glutamates; D006710:Homocysteine; C007956:homocysteic acid; D010768:Phosphoserine; D012694:Serine; C036040:serine O-sulfate; C012729:2-amino-4-phosphonobutyric acid