Pharmacological similarity between the retinal APB receptor and the family of metabotropic glutamate receptors.

1. We performed current-clamp and voltage-clamp experiments in the amphibian retina to examine the effects of 1-amino-1,3-cyclopentanedicarboxylic acid (1S,3R ACPD), which is a selective agonist for the family of metabotropic glutamate receptors. 2. 1S,3R ACPD was found to selectively block the light responses of ON bipolar cells. It did not suppress the responses of horizontal cells of OFF bipolar cells. It blocked ON but not OFF responses of third-order retinal neurons. 3. 1S,3R ACPD mimicked the effect of the photoreceptor transmitter at the ON bipolar synapse. It reduced an inward current by a decrease in conductance. 4. The action of 1S,3R ACPD was very similar to that of 2-amino-4-phosphonobutyrate (APB) both in terms of effects on the ON bipolar cell potential and conductance and in terms of the retinal network. This suggests that the APB receptor is a predominant synaptic metabotropic glutamate receptor in the retina. 5. The rank-order potency at the retinal APB receptor is APB > 1S,3R ACPD > ibotenate. Quisqualate appears to be inactive at this receptor. The pharmacology of the retinal APB receptor matches that of the cloned mGluR4 and mGluR6 metabotropic glutamate receptors. On the basis of the in situ localization of mGluR6 to the inner nuclear layer of the retina, the retinal APB receptor may be this cloned receptor protein. 6. The effects of the three other ACPD stereo isomers were examined. 1S,3S ACPD was a weak agonist at the APB receptor. 1R,3R ACPD was a potent agonist in the inner retina, but inactive in the outer retina. This fits the profile of N-methyl-D-aspartate agonists. 1R,3S ACPD was inactive.