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- Title
Differential modulation of human GABA<sub>C</sub>-ρ1 receptor by sulfur-containing compounds structurally related to taurine.
- Authors
Ochoa-de la Paz, Lenin David; González-Andrade, Martin; Pasantes-Morales, Herminia; Franco, Rodrigo; Zamora-Alvarado, Rubén; Zenteno, Edgar; Quiroz-Mercado, Hugo; Gonzales-Salinas, Roberto; Gulias-Cañizo, Rosario
- Abstract
<bold>Background: </bold>The amino acid taurine (2-Aminoethanesulfonic acid) modulates inhibitory neurotransmitter receptors. This study aimed to determine if the dual action of taurine on GABAC-ρ1R relates to its structure. To address this, we tested the ability of the structurally related compounds homotaurine, hypotaurine, and isethionic acid to modulate GABAC-ρ1R.<bold>Results: </bold>In Xenopus laevis oocytes, hypotaurine and homotaurine partially activate heterologously expressed GABAC-ρ1R, showing an increment in its deactivation time with no changes in channel permeability, whereas isethionic acid showed no effect. Competitive assays suggest that hypotaurine and homotaurine compete for the GABA-binding site. In addition, their effects were blocked by the ion-channel blockers picrotixin and Methyl(1,2,5,6-tetrahydropyridine-4-yl) phosphinic acid. In contrast to taurine, co-application of GABA with hypotaurine or homotaurine revealed that the dual effect is present separately for each compound: hypotaurine modulates positively the GABA current, while homotaurine shows a negative modulation, both in a dose-dependent manner. Interestingly, homotaurine diminished hypotaurine-induced currents. Thus, these results strongly suggest a competitive interaction between GABA and homotaurine or hypotaurine for the same binding site. "In silico" modeling confirms these observations, but it also shows a second binding site for homotaurine, which could explain the negative effect of this compound on the current generated by GABA or hypotaurine, during co-application protocols.<bold>Conclusions: </bold>The sulfur-containing compounds structurally related to taurine are partial agonists of GABAC-ρ1R that occupy the agonist binding site. The dual effect is unique to taurine, whereas in the case of hypotaurine and homotaurine it presents separately; hypotaurine increases and homotaurine decreases the GABA current.
- Subjects
GABA receptors; SULFUR compounds; TAURINE; AMINO acids; XENOPUS laevis
- Publication
BMC Neuroscience, 2018, Vol 19, Issue 1, pN.PAG
- ISSN
1471-2202
- Publication type
journal article
- DOI
10.1186/s12868-018-0448-6