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Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs

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Abstract

Taurine activates and modulates GABA receptors in vivo as well as those expressed in heterologous systems. This study aimed to determine whether the structural analogs of taurine: homotaurine and hypotaurine, have the ability to activate GABA-A receptors that include GABAρ subunits. The expression of GABA-A receptors containing GABAρ has been reported in the STC-1 cells and astrocytes. In both cell types, taurine, homo-, and hypotaurine gated with low efficiency a picrotoxin-sensitive GABA-A receptor. The known bimodal modulatory effect of taurine on GABAρ receptors was not observed; however, differences between the activation and deactivation rates were detected when they were perfused together with GABA. In silico docking simulations suggested that taurine, hypo-, and homotaurine do not form a cation–π interaction such as that generated by GABA in the agonist-binding site of GABAρ. This observation complements the electrophysiological data suggesting that taurine and its analogs act as partial agonists of GABA-A receptors. All the observations above suggest that the structural analogs of taurine are partial agonists of GABA-A receptors that occupy the agonist-binding site, but their structures do not allow the proper interaction with the receptor to fully gate its Cl− channel.

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Abbreviations

DMEM:

Dulbecco’s modified eagle’s medium

FBS:

Fetal bovine serum

GABA:

γ-amminobutyric acid

GLIC:

Gloebacter ion channel

EGTA:

Ethylene glycol tetraacetic acid

GluCl:

Glutamate-gated ion channel

HEPES:

2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid

ICM:

Internal coordinate mechanics

RsT:

Rise time constant

STC-1:

Secretin tumor cell line

TPMPA:

(1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid

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Acknowledgments

We thank E. Ruiz Alcíbar and A. E. Espino Saldaña for technical support and Dr. Dorothy Pless for reviewing the manuscript. This work was supported by grants from CONACYT (220224 and 166964), PAPIIT-UNAM (IN206411, 205308, RR280412-2, 200913), and IACOD-UNAM (IA202411-22).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Departamento de Neurobiología Celular y Molecular, Laboratorio de Neurobiología Molecular y Celular, Instituto de Neurobiología, Campus UNAM Juriquilla, CP 76230, Querétaro, QRO, Mexico

    Daniel Reyes-Haro, Elizabeth Cabrera-Ruíz, Argel Estrada-Mondragón, Ricardo Miledi & Ataúlfo Martínez-Torres

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  1. Daniel Reyes-Haro
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  2. Elizabeth Cabrera-Ruíz
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  3. Argel Estrada-Mondragón
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  4. Ricardo Miledi
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  5. Ataúlfo Martínez-Torres
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Correspondence to Ataúlfo Martínez-Torres.

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Reyes-Haro, D., Cabrera-Ruíz, E., Estrada-Mondragón, A. et al. Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs. Amino Acids 46, 2587–2593 (2014). https://doi.org/10.1007/s00726-014-1813-0

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  • DOI: https://doi.org/10.1007/s00726-014-1813-0

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