2 PHENYLGLYCINE DERIVATIVES ANTAGONIZE RESPONSES TO L-AP4 IN ON BIPOLAR CELLS OF THE AMPHIBIAN RETINA

Light responses of retinal ON bipolar cells are mediated by metabotrop ic glutamate receptors selectively activated by L-2-amino-4-phosphonob utyric acid (L-AP4). Antagonists to L-AP4 receptors in ON bipolar cell s have not previously been identified. This study examines the electro physiological 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 ce lls of the amphibian retina. Unlike its actions in spinal cord, in ret inal ON bipolar cells MAP4 is a weak agonist which exhibits no detecta ble antagonism to L-AP4. On the other hand, CDHPG exhibits a mixture o f agonist and antagonist properties. Addition of Co2+ and oxygenation of CDHPG turns the solution brown and enhances antagonist effects, sug gesting that the antagonism reflects actions of a breakdown product of CDHPG. Although THPG did not prove to be this breakdown product, it a lso has electrophysiological effects consistent with an L-AP4 receptor antagonist. The results suggest that THPG and breakdown products of C DHPG 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 rece ptors cannot yet be excluded. (C) 1997 Elsevier Science Ltd.