Dopamine and Serotonin Modulate Human GABAρ1 Receptors Expressed in Xenopus laevis Oocytes

Abstract

GABAρ1 receptors are highly expressed in bipolar neurons of the retina and to a lesser extent in several areas of the central nervous system (CNS), and dopamine and serotonin are also involved in the modulation of retinal neural transmission. Whether these biogenic amines have a direct effect on ionotropic GABA receptors was not known. Here, we report that GABAρ1 receptors, expressed in X. laevis oocytes, were negatively modulated by dopamine and serotonin and less so by octopamine and tyramine. Interestingly, these molecules did not have effects on GABA(A) receptors. 5-Carboxamido-tryptamine and apomorphine did not exert evident effects on any of the receptors. Schild plot analyses of the inhibitory actions of dopamine and serotonin on currents elicited by GABA showed slopes of 2.7 ± 0.3 and 6.1 ± 1.8, respectively, indicating a noncompetitive mechanism of inhibition. The inhibition of GABAρ1 currents was independent of the membrane potential and was insensitive to picrotoxin, a GABA receptor channel blocker and to the GABAρ-specific antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl phosphinic acid (TPMPA). Dopamine and serotonin changed the sensitivity of GABAρ1 receptors to the inhibitory actions of Zn(2+). In contrast, La(3+) potentiated the amplitude of the GABA currents generated during negative modulation by dopamine (EC(50) 146 μM) and serotonin (EC(50) 196 μM). The functional role of the direct modulation of GABAρ receptors by dopamine and serotonin remains to be elucidated; however, it may represent an important modulatory pathway in the retina, where GABAρ receptors are highly expressed and where these biogenic amines are abundant.

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

“…As a consequence of this effect, dopamine relieved the GABAergic inhibition on the activity of third order retinal neurons. Consistent with these results is a recent finding that dopamine exerts a direct noncompetitive inhibition of human GABA ρ , but not GABA A receptors, expressed in Xenopus laevis oocytes [7]. The authors proposed that “the binding site for dopamine in GABAρ 1 receptor is different from the GABA binding site, and is probably not located inside the channel pore”.…”

Interactions between the Serotoninergic System and the Ionotropic GABA Receptors in Frog and Turtle Retina: An Immunofluorescent Study

“…We succeeded to prove the idea that serotonin could decrease the activity of GABA receptors, predominantly GABA C ones, which regulate the output of the main retinal neurons, the bipolar cells. In such a way, our results confirm the idea that serotonin can negatively modulate the GABA ρ receptors expression in Xenopus laevis oocytes [13]. Our results are in agreement with the data of some other authors who also showed reciprocal relations between the two systems in different brain regions [26,27].…”

“…The aim of our study is to elucidate the putative interactions between these two retinal neurotransmitters systems. Based on the Ochoa-de la Paz et al's experiments, which showed that dopamine and serotonin may modulate negatively the GABA rho1 receptor expression in Xenopus laevis oocytes [13], we decided to study the interactions between serotonin -from one side, and the ionotropic GABA receptors -from other, in the retinas of the frog (Rana ridibunda) and the turtle (Pseudemys elegans). While the frog, a representative of class Amphybia, possesses mixed type of retina where both rod and cone photoreceptors are present, the turtle -belonging to class Reptilia, has predominantly cones in its retina.…”

Tryptophan Hydroxylase and Serotonin Receptors 5-HT1A, 5-HT2A, 5-HT3A, 5-HT4, 5-HT5A, 5-HT6 and 5-HT7 in Frog and Turtle Retina: an Immunofluorescence Study

“…Taking into account the large number of serotonin receptors spread in the INL, it may be supposed that serotonin released by the retinopetal axons freely diffuses and binds to these receptors, exerting its effect as a neuromodulator. The negative neuromodulatory effect of serotonin on GABA ρ1 receptors has already been demonstrated on Xenopus laevis oocytes [61]. This is in conjunction with our understanding that serotonin serves not only as a neurotransmitter, but as a neuromodulator of the retinal function as well.…”