Effects of dopamine D1 receptor blockade on the ERG b- and d-waves during blockade of ionotropic GABA receptors.

Momchil Kostov,Petia Kupenova,Elka Popova

doi:10.1186/s40662-016-0064-4

Momchil Kostov, Petia Kupenova + Show 1 more

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https://doi.org/10.1186/s40662-016-0064-4

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Abstract

BackgroundSome data indicate that the dopaminergic and GABAergic systems interact in the vertebrate retina, but the type of interactions is not well understood.MethodsIn this study we investigated the effect of dopamine D1 receptor blockade by 75 μM SCH 23390 on the electroretinographic ON (b-wave) and OFF (d-wave) responses in intact frog eyecup preparations and in eyecups where the ionotropic GABA receptors were blocked by 50 μM picrotoxin. Student’s t-test, One-way repeated measures ANOVA with Bonferroni post-hoc test and Two-way ANOVA were used for statistical evaluation of the data.ResultsWe found that SCH 23390 alone significantly enhanced the amplitude of the b- and d-waves without altering their latency. The effect developed rapidly and was fully expressed within 8-11 min after the blocker application. Picrotoxin alone also markedly enhanced the amplitude of the ERG ON and OFF responses and increased their latency significantly. The effect was fully expressed within 25-27 min after picrotoxin application and remained very stable in the next 20 min. The effects of SCH 23390 and picrotoxin are similar to that reported in our previous studies. When SCH 23390 was applied on the background of the fully developed picrotoxin effect, it diminished the amplitude of the b- and d-waves in comparison to the corresponding values obtained during application of picrotoxin alone.ConclusionOur results demonstrate that the enhancing effect of D1 receptor blockade on the amplitude of the ERG b- and d-waves is not evident during the ionotropic GABA receptor blockade, indicating an interaction between these neurotransmitter systems in the frog retina. We propose that the inhibitory effect of endogenous dopamine mediated by D1 receptors on the ERG ON and OFF responses in the frog retina may be due to the dopamine-evoked GABA release.Electronic supplementary materialThe online version of this article (doi:10.1186/s40662-016-0064-4) contains supplementary material, which is available to authorized users.

Highlights

Some data indicate that the dopaminergic and GABAergic systems interact in the vertebrate retina, but the type of interactions is not well understood
In this study we investigated the effect of dopamine D1 receptor blockade with SCH 23390 on the ERG b- and d-waves in intact frog eyecup preparations and in eyecups where the ionotropic GABA receptors were blocked by picrotoxin
Perfusion with SCH 23390 did not significantly alter the latency of the ERG waves (Table 1). These results are consistent with our previous findings in the dark adapted frog retina [15, 16] and indicate that endogenous dopamine acting through D1 receptors has a suppressive action on the amplitude of the ERG ON and OFF responses

Summary

Introduction

Some data indicate that the dopaminergic and GABAergic systems interact in the vertebrate retina, but the type of interactions is not well understood. Some authors reported that dopamine and D1 receptor agonist SKF 38393 increased the GABA-induced currents in rat retinal amacrine cells through phosphorylation of GABAA receptors by PKA [4]. Dopamine and D1 receptor agonist SKF 38393 relieved the GABAergic inhibition, mediated mainly (but not entirely) by GABAC receptors, of calcium entry in most bipolar cell terminals in the tiger salamander retina [6]. The authors proposed that “the binding site for dopamine in GABAρ1 receptor is different from the GABA binding site, and is probably not located inside the channel pore”. It appears that dopamine may have opposite effects on the currents mediated by GABAA and GABAρ receptors in single retinal neurons

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