L-2-amino-3-phosphonopropionic acid competitively antagonizes metabotropic glutamate receptors 1α and 5 in Xenopus oocytes

Julie Saugstad, Thomas P. Segerson, Gary Westbrook

Research output: Contribution to journalArticle

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Abstract

The aspartate analog 2-amino-3-phosphonopropionic acid (AP3) antagonizes glutamate-stimulated phosphatidyl inositide hydrolysis in brain slices, but is reportedly weak or ineffective in antagonizing the phosphatidyl inositide-coupled cloned metabotropic glutamate receptors 1α and 5. Thus we examined the pharmacological properties of AP3 on mGlu and mGlu5 receptor responses in Xenopus oocytes. DL-AP3 antagonized mGlu and mGlu5 responses, but antagonism was overcome at high glutamate concentrations consistent with competitive inhibition (IC50 = 2.1 nM for mGlu). Both responses were also inhibited by (RS)-α-methyl-4-carboxyphenylglycine (MCPG). We conclude that the available antagonists cannot distinguish between the mGlu receptor and mGlu5 receptor, and that antagonism by AP3 may be obscured in the presence of high agonist concentrations or in cells with spare receptors.

Original languageEnglish (US)
Pages (from-to)395-397
Number of pages3
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume289
Issue number2
DOIs
Publication statusPublished - Apr 28 1995

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Keywords

  • L-AP3 (L-2-amino-3-phosphonopropionic acid)
  • MCPG ((RS)-α-methyl-4-carboxyphenylglycine)
  • Metabotropic glutamate receptor
  • Phosphatidyl inositide hydrolysis
  • Xenopus oocyte

ASJC Scopus subject areas

  • Pharmacology

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