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

Neuropharmacology. 1997 Jan;36(1):13-20. doi: 10.1016/s0028-3908(96)00164-5.


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)-4-4-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminobutyrates / pharmacology*
  • Animals
  • Excitatory Amino Acid Agents / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Light
  • Necturus maculosus
  • Patch-Clamp Techniques
  • Phenylacetates / pharmacology*
  • Receptors, Glutamate / drug effects*
  • Retina / drug effects*


  • 2-amino-2-methyl-4-phosphonobutyrate
  • 2-amino-4-phosphonobutanoic acid receptor
  • 3,4,5-trihydroxyphenylglycine
  • Aminobutyrates
  • Excitatory Amino Acid Agents
  • Phenylacetates
  • Receptors, Glutamate
  • 2-amino-4-phosphonobutyric acid
  • Glycine