The glutamate analog 2-amino-4-phosphonobutyrate antagonizes synaptic transmission from cones to horizontal cells in the goldfish retina.

Abstract

In the retina, the glutamate analog 2-amino-

Group III Metabotropic Glutamate Receptors and Exocytosed Protons Inhibit L-Type Calcium Currents in Cones But Not in Rods

“…This is compatible with the observation that L-AP-4 reduced cone-dominated light responses of the second-order neurons in carp and tiger salamander retinas (Nawy et al, 1989;Hare and Owen, 1992;Hirasawa et al, 2002). Furthermore, we identified the cone L-type I Ca as the target of presynaptic group III mGluR action.…”

“…Koulen et al (1999) have recently shown that another group III mGluR, mGluR8, is distributed in photoreceptor terminals in the rat retina and that activation of mGluR8 decreases the intracellular calcium concentrations in dissociated photoreceptors, although underlying mechanisms of the calcium regulation were not identified in their study. It has been reported that the group III mGluR-specific agonist L-2-amino-4-phosphonobutyric acid (L-AP-4) not only blocks the ON signal but also reduces light responses of OFF bipolar cells and cone horizontal cells (Nawy et al, 1989;Hare and Owen, 1992;Hirasawa et al, 2002). However, simultaneous activation of many different types of neurons in retinal circuits by light stimulation compromises interpretation of changes in photoresponses.…”

Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.

“…In initial attempts, concentrations of glutamate (200-400 /SM) which depressed synaptic transmission caused an inward current making the measurement of the EPSC unreliable. Because the NMDA receptor has a much higher affinity for glutamate than ionotropic non-NMDA receptors (Collingridge & Lester, 1989) & Watkins, 1982;Harris & Cotman, 1983;Cotman et al 1986;Nawy, Sie & Copenhagen, 1989;Forsythe & Clements, 1990), a structurally similar, phosphonic derivative of glutamate (Collingridge & Lester, 1989;Monaghan et al 1989). L-AP4 has also been reported to stimulate PI turnover (Schoepp et al 1990) it can interact with metabotropic glutamate receptors.…”

“…Presynaptic glutamate receptors activated by L-AP4 have been shown to inhibit excitatory synaptic transmission at several other synapses (Koerner & Cotman, 1981;Davies & Watkins, 1982;Harris & Cotman, 1983;Cotman et al 1986;Nawy et al 1989;Forsythe & Clements, 1990). It will be interesting to determine whether, as these synapses, metabotropic glutamate receptor agonists have similar inhibitory actions on synaptic transmission.…”

Primate Retinal Signaling Pathways: Suppressingon-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYXGenetic Night Blindness

“…Hence it is unlikely that much of the CSNB1-NYX amplitude reduction at higher frequencies results from a lack of photoreceptor amplitude. It is possible, however, that APB and PDA may also have effects elsewhere in the retina including horizontal cell feedback onto photoreceptors in some species (Massey 1995;Nawy 1989;Yang 1989). Blocking horizontal cell feedback could reduce photoreceptor flicker amplitude in vivo.…”