title: Two phenylglycine derivatives antagonize responses to L-AP4 in ON bipolar cells of the amphibian retina.
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)-4-4-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.
authors.affiliation: Department of Ophthalmology, University of Nebraska Medical Center, Omaha 68198-5540, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Thoreson
authors.forename: J
authors.initials: J
authors.lastname: Gottesman
authors.forename: D E
authors.initials: DE
authors.lastname: Jane
authors.forename: H W
authors.initials: HW
authors.lastname: Tse
authors.forename: J C
authors.initials: JC
authors.lastname: Watkins
authors.forename: R F
authors.initials: RF
authors.lastname: Miller
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008027:Light; D009338:Necturus maculosus; D018408:Patch-Clamp Techniques; D010648:Phenylacetates / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000187:drug effects*; D012160:Retina / Q000187:drug effects*
chemical_list: C089836:2-amino-2-methyl-4-phosphonobutyrate; C074680:2-amino-4-phosphonobutanoic acid receptor; C107236:3,4,5-trihydroxyphenylglycine; D000613:Aminobutyrates; D018683:Excitatory Amino Acid Agents; D010648:Phenylacetates; D017470:Receptors, Glutamate; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine