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

Lenin D. Ochoa-De La Paz, Argel Estrada-Mondragón, Agenor Limon-Ruiz, Ricardo Miledi, Ataúlfo Martínez-Torres

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)96-104
Number of pages9
JournalACS Chemical Neuroscience
Volume3
Issue number2
DOIs
StatePublished - Feb 15 2012
Externally publishedYes

Fingerprint

Xenopus laevis
Oocytes
Dopamine
Serotonin
GABA Receptors
gamma-Aminobutyric Acid
Biogenic Amines
Modulation
Retina
Phosphinic Acids
Octopamine
GABA Antagonists
Picrotoxin
Tyramine
Apomorphine
Neurology
GABA-A Receptors
Synaptic Transmission
Membrane Potentials
Neurons

Keywords

  • 5-HT
  • dopamine
  • GABAρ1
  • GABA
  • receptor modulation
  • Xenopus oocyte

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

Cite this

Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes. / Ochoa-De La Paz, Lenin D.; Estrada-Mondragón, Argel; Limon-Ruiz, Agenor; Miledi, Ricardo; Martínez-Torres, Ataúlfo.

In: ACS Chemical Neuroscience, Vol. 3, No. 2, 15.02.2012, p. 96-104.

Research output: Contribution to journalArticle

Ochoa-De La Paz, LD, Estrada-Mondragón, A, Limon-Ruiz, A, Miledi, R & Martínez-Torres, A 2012, 'Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes', ACS Chemical Neuroscience, vol. 3, no. 2, pp. 96-104. https://doi.org/10.1021/cn200083m
Ochoa-De La Paz, Lenin D. ; Estrada-Mondragón, Argel ; Limon-Ruiz, Agenor ; Miledi, Ricardo ; Martínez-Torres, Ataúlfo. / Dopamine and serotonin modulate human GABAρ1 receptors expressed in Xenopus laevis oocytes. In: ACS Chemical Neuroscience. 2012 ; Vol. 3, No. 2. pp. 96-104.
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