Characterization of retinal and hippocampal l-AP4 receptors using conformationally constrained AP4 analogues

N. L. Peterson, Wallace B Thoreson, R. L. Johnson, J. F. Koerner, R. F. Miller

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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)-amino-3-phosphonocycolohexanecarboxylic 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)-cycloprophy; 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 a acid/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (KAIN/AMPA) pathways and one N-methyl-d-aspartate (NMDA) hippocampal pathways 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.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalBrain Research
Volume568
Issue number1-2
DOIs
StatePublished - Dec 24 1991

Fingerprint

Kainic Acid
Pharmacology
Aspartic Acid
Acids
2-amino-4-phosphonobutanoic acid receptor
bucide
propionic acid

Keywords

  • Electroretinogram
  • Hippocampus
  • ON-bipolar cell
  • l-2-Amino-4-phosphonobutanoic acid
  • l-2-Amino-4-phosphonobutanoic acid receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Characterization of retinal and hippocampal l-AP4 receptors using conformationally constrained AP4 analogues. / Peterson, N. L.; Thoreson, Wallace B; Johnson, R. L.; Koerner, J. F.; Miller, R. F.

In: Brain Research, Vol. 568, No. 1-2, 24.12.1991, p. 15-23.

Research output: Contribution to journalArticle

Peterson, N. L. ; Thoreson, Wallace B ; Johnson, R. L. ; Koerner, J. F. ; Miller, R. F. / Characterization of retinal and hippocampal l-AP4 receptors using conformationally constrained AP4 analogues. In: Brain Research. 1991 ; Vol. 568, No. 1-2. pp. 15-23.
@article{6822d2e3ab9749c2ab237bbff78fd436,
title = "Characterization of retinal and hippocampal l-AP4 receptors using conformationally constrained AP4 analogues",
abstract = "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)-amino-3-phosphonocycolohexanecarboxylic 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)-cycloprophy; 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 a acid/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (KAIN/AMPA) pathways and one N-methyl-d-aspartate (NMDA) hippocampal pathways 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.",
keywords = "Electroretinogram, Hippocampus, ON-bipolar cell, l-2-Amino-4-phosphonobutanoic acid, l-2-Amino-4-phosphonobutanoic acid receptor",
author = "Peterson, {N. L.} and Thoreson, {Wallace B} and Johnson, {R. L.} and Koerner, {J. F.} and Miller, {R. F.}",
year = "1991",
month = "12",
day = "24",
doi = "10.1016/0006-8993(91)91374-A",
language = "English (US)",
volume = "568",
pages = "15--23",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Characterization of retinal and hippocampal l-AP4 receptors using conformationally constrained AP4 analogues

AU - Peterson, N. L.

AU - Thoreson, Wallace B

AU - Johnson, R. L.

AU - Koerner, J. F.

AU - Miller, R. F.

PY - 1991/12/24

Y1 - 1991/12/24

N2 - 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)-amino-3-phosphonocycolohexanecarboxylic 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)-cycloprophy; 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 a acid/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (KAIN/AMPA) pathways and one N-methyl-d-aspartate (NMDA) hippocampal pathways 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.

AB - 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)-amino-3-phosphonocycolohexanecarboxylic 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)-cycloprophy; 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 a acid/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (KAIN/AMPA) pathways and one N-methyl-d-aspartate (NMDA) hippocampal pathways 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.

KW - Electroretinogram

KW - Hippocampus

KW - ON-bipolar cell

KW - l-2-Amino-4-phosphonobutanoic acid

KW - l-2-Amino-4-phosphonobutanoic acid receptor

UR - http://www.scopus.com/inward/record.url?scp=0026332954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026332954&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(91)91374-A

DO - 10.1016/0006-8993(91)91374-A

M3 - Article

VL - 568

SP - 15

EP - 23

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -