Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes

Ochoa-de la Paz, Lenin D., Estrada-Mondragón, Argel, Limón, Agenor, Miledi, Ricardo and Martínez-Torres, Ataúlfo (2012) Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes. ACS Chemical Neuroscience, 3 2: 96-104. doi:10.1021/cn200083m

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Author Ochoa-de la Paz, Lenin D.
Estrada-Mondragón, Argel
Limón, Agenor
Miledi, Ricardo
Martínez-Torres, Ataúlfo
Title Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes
Formatted title
Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes
Journal name ACS Chemical Neuroscience   Check publisher's open access policy
ISSN 1948-7193
Publication date 2012-02-15
Sub-type Article (original research)
DOI 10.1021/cn200083m
Open Access Status
Volume 3
Issue 2
Start page 96
End page 104
Total pages 9
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
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 GABAA 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 Zn2+. In contrast, La 3+ potentiated the amplitude of the GABA currents generated during negative modulation by dopamine (EC50 146 μM) and serotonin (EC50 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.
Keyword GABAρ1
GABAA
Dopamine
Receptor modulation
5-HT
Xenopus Oocyte
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Thu, 04 Sep 2014, 09:03:59 EST by Argel Estrada on behalf of Queensland Brain Institute