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- W2028984161 abstract "Hippocampal CA1 pyramidal cell neurons are sensitized to depolarization byl-2-amino-4-phosphonobutanoic acid (l-AP4) following exposure tol-quisqualic acid (QUIS). We have examined the interaction of 43 structural analogues ofl-AP4 with both the ‘induction’ site and the QUIS-sensitive AP4 site in rat hippocampus. The synthesis ofcis- andtrans-4-phosphonoxyl-l-proline, 3-(RS)-amino-5-phosphonopentanoic acid and 2(RS)-amino-5-phenyl-4(RS)-phosphonopentanoic acid (γ-benzyl AP4) are described. None of the test compounds interact with the induction site; thusl-QUIS remains the only compound known to induce this effect. However, one compound (l-2-amino-3-(5-tetrazolyl) -propanoic acid (l-aspartate tetrazole) ‘pre-blocked’ and reversed the effects of QUIS. In addition, the potency of 16 analogues increased more than 4-fold following exposure of slices tol-QUIS. Among these,l-AP4,l-AP5, 2-amino-4-(methylphosphino) butanoic acid (AMPB), andE-1(RS)-amino-3(RS)-phosphonocyclopentanecar☐ylic acid (E-cyclopentyl AP4) diplayed IC50 values of less than 0.100mM after QUIS. The results presented here suggest that the QUIS-sensitive AP4 site requires a spatial configuration of functional groups similar to that present inE-cyclopentyl AP4. The presence of a primary amino group and a phosphorus-containing group (either monoanionic or dianionic) appear to be required, however, a car☐yl group is not essential for interaction. The pharmacology of the QUIS-sensitive AP4 site suggest that it is distinct from other known binding sites forl-AP4 in the central nervous system (CNS)." @default.
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- W2028984161 date "1992-06-01" @default.
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- W2028984161 title "Structure-function relationships for analogues ofl-2-amino-4-phosphonobutanoic acid on the quisqualic acid-sensitive AP4 receptor of the rat hippocampus" @default.
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- W2028984161 doi "https://doi.org/10.1016/0006-8993(92)90146-z" @default.
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