Two phenylglycine derivatives antagonize responses to L-AP4 in ON bipolar cells of the amphibian retina

Wallace B Thoreson, J. Gottesman, D. E. Jane, Heong Wai Tse, J. C. Watkins, R. F. Miller

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Abstract

Light responses of retinal ON bipolar cells are mediated by metabotropic glutamate receptors selectively activated by L-2-amino-4-phosphonobutyric acid (L-AP4). Antagonists to L-AP4 receptors in ON bipolar cells have not previously been identified. This study examines the electrophysiological effects of (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), (RS)-4-chloro-3,5-dihydroxyphenylglycine (CDHPG) and (RS)-3,4,5-trihydroxyphenylglycine (THPG), at L-AP4 receptors in ON bipolar cells of the amphibian retina. Unlike its actions in spinal cord, in retinal ON bipolar cells MAP4 is a weak agonist which exhibits no detectable antagonism to L-AP4. On the other hand, CDHPG exhibits a mixture of agonist and antagonist properties. Addition of Co2+ and oxygenation of CDHPG turns the solution brown and enhances antagonist effects, suggesting that the antagonism reflects actions of a breakdown product of CDHPG. Although THPG did not prove to be this breakdown product, it also has electrophysiological effects consistent with an L-AP4 receptor antagonist. The results suggest that THPG and breakdown products of CDHPG may be antagonists to L-AP4 receptors in retinal ON bipolar cells, although the possibility that these compounds antagonize effects of L-AP4 by acting at some site in the transduction pathway of L-AP4 receptors cannot yet be excluded.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalNeuropharmacology
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 1 1997

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Keywords

  • L-2-amino-4-phosphonobutyric acid
  • metabotropic glutamate receptors
  • phenylglycine
  • retinal ON bipolar cells

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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