Synthesis of [3H]2-Amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes: a selective ligand for the chloride/calcium-dependent class of l-glutamate binding sites

Daniel T. Monaghan, M. C. McMills, A. Richard Chamberlin, Carl W. Cotman

Research output: Contribution to journalArticle

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[3H]2-amino-4-phosphonobutyric acid was synthesized by the conjugate addition of 1-lithio-2-trimethylsilyethyne to diethyl ethynylphosphate followed by catalytic tritiation and hydrolysis. Radiolabelled 2-amino-4-phosphonobutyric acid binds to a distinct class of l-glutamate binding sites and does not exhibit appreciable binding to sites not displaced by l-glutamate. The binding affinity (Kd = 5.1 ± 0.4 μM) and pharmacological profile correspond to those values obtained from physiological studies of 2-amino-4-phosphonobutyric acid inhibition of synaptic transmission, and to those values obtained in [3H]l-glutamate binding assays. [3H]2-amino-4-phosphonobutyric acid does not exhibit significant binding to the Cl-/Ca2+-independent l-glutamate binding site(s), nor to the Na+-dependent l-glutamate binding site (up to 50 mM Na+). These data provide further evidence that the physiological action of 2-amino-4-phosphonobutyric acid is mediated by the previously described Cl-/Ca2+-dependent l glutamate binding sites, and provides an assay system which is optimal for the study of these sites.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalBrain Research
Issue number1-2
Publication statusPublished - Nov 14 1983



  • 2-amino-4-phosphonobutyric acid
  • excitatory amino acids
  • glutamate receptors

ASJC Scopus subject areas

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

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