title: Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs.
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.
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Laboratorio de Neurobiología Molecular y Celular, Instituto de Neurobiología, Campus UNAM Juriquilla, CP 76230, Querétaro, QRO, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Reyes-Haro
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cabrera-Ruíz
authors.forename: Argel
authors.initials: A
authors.lastname: Estrada-Mondragón
authors.forename: Ricardo
authors.initials: R
authors.lastname: Miledi
authors.forename: Ataúlfo
authors.initials: A
authors.lastname: Martínez-Torres
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001665:Binding Sites; D017173:Caenorhabditis elegans; D002460:Cell Line; D003198:Computer Simulation; D004594:Electrophysiology; D006801:Humans; D007700:Kinetics; D008024:Ligands; D051379:Mice; D018408:Patch-Clamp Techniques; D010477:Perfusion; D010852:Picrotoxin / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011963:Receptors, GABA-A / Q000737:chemistry*; D013654:Taurine / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D008024:Ligands; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013654:Taurine; C001355:tramiprosate; C003949:hypotaurine