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Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation.

1992; Springer Nature; Volume: 11; Issue: 6 Linguagem: Inglês

10.1002/j.1460-2075.1992.tb05259.x

1460-2075

Volker Schmieden, Jochen Kuhse, Heinrich Betz,

Neuroendocrine regulation and behavior

Research Article1 June 1992free access Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation. V. Schmieden V. Schmieden Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. Search for more papers by this author J. Kuhse J. Kuhse Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. Search for more papers by this author H. Betz H. Betz Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. Search for more papers by this author V. Schmieden V. Schmieden Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. Search for more papers by this author J. Kuhse J. Kuhse Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. Search for more papers by this author H. Betz H. Betz Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. Search for more papers by this author Author Information V. Schmieden1, J. Kuhse1 and H. Betz1 1Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt am Main, FRG. The EMBO Journal (1992)11:2025-2032https://doi.org/10.1002/j.1460-2075.1992.tb05259.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The inhibitory glycine receptor (GlyR) is a pentameric chloride channel protein which mediates postsynaptic inhibition in the mammalian central nervous system. In spinal cord, different GlyR isoforms originate from the sequential expression of developmentally regulated variants of the ligand binding alpha subunit. Here, neonatal alpha 2 and adult alpha 1 subunits are shown to generate GlyRs with distinct agonist activation profiles upon heterologous expression in Xenopus oocytes. Whereas alpha 1 receptors are efficiently gated by beta-alanine and taurine, alpha 2 GlyRs show only a low relative response to these agonists, which also display a reduced sensitivity to inhibition by the glycinergic antagonist strychnine. Construction of an alpha 2/alpha 1 subunit chimera and site-directed mutagenesis of the extracellular region of the alpha 1 sequence identified amino acid positions 111 and 212 as important determinants of taurine activation. Our results indicate the existence of distinct subsites for agonists on alpha 1 and alpha 2 GlyRs and suggest that the ligand binding pocket of these receptor proteins is formed from discontinuous domains of their extracellular region. Previous ArticleNext Article Volume 11Issue 61 June 1992In this issue RelatedDetailsLoading ...