Characterization of retinal and hippocampal L- AP4 receptors using conformationally constrained AP4 analogues.
In the past, the absence of useful 2-amino-4-phosphonobutanoic acid ( AP4) analogues has hampered the pharmacological study and comparison of different systems which are sensitive to L- AP4. Several conformationally constrained AP4 analogues have now been synthesized: (E)- and (Z)-1-amino-3-phosphonocyclopentanecarboxylic acid [(E)- and (Z)-cyclopentyl AP4], and (E)- and (Z)-1-amino-3-phosphonocyclohexanecarboxylic acid [(E)- and (Z)-cyclohexyl AP4], and the recently synthesized cyclopropyl analogues (E)- and (Z)-2-amino-2,3-methano-4-phosphonobutanoic acid [(E)- and (Z)-cyclopropyl AP4]. Therefore, we have examined and report here the pharmacology of two retinal and two hippocampal L- AP4 sensitive systems using these analogues. In addition, the pharmacology of two kainic acid/alpha-amino-3-hydroxy-5-methylisoxazole-4- propionic acid (KAIN/AMPA) pathways and one N-methyl-D-aspartate (NMDA) hippocampal pathway was examined. We found that the rank order potency of the L- AP4 sensitive systems were similar though not identical. The KAIN/AMPA and NMDA systems had a quite different rank order of potencies than the L- AP4 systems. These data suggest that the L- AP4 receptors in these different systems are structurally similar to each other and differ from both KAIN/AMPA and NMDA receptors.[1]References
- Characterization of retinal and hippocampal L-AP4 receptors using conformationally constrained AP4 analogues. Peterson, N.L., Thoreson, W.B., Johnson, R.L., Koerner, J.F., Miller, R.F. Brain Res. (1991) [Pubmed]
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