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.
Peterson
N L
NL
Department of Biochemistry, University of Minnesota, Minneapolis 55455.
Thoreson
W B
WB
Johnson
R L
RL
Koerner
J F
JF
Miller
R F
RF
D000613:Aminobutyrates / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D006624:Hippocampus / Q000378:metabolism*; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D013329:Structure-Activity Relationship
C074680:2-amino-4-phosphonobutanoic acid receptor; D000613:Aminobutyrates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C012729:2-amino-4-phosphonobutyric acid