@article {Supplisson763, author = {Stephane Supplisson and Dominique Chesnoy-Marchais}, title = {Glycine Receptor β Subunits Play a Critical Role in Potentiation of Glycine Responses by ICS-205,930}, volume = {58}, number = {4}, pages = {763--770}, year = {2000}, doi = {10.1124/mol.58.4.763}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The sensitivity of various types of recombinant glycine receptors (GlyRs) to ICS-205,930 was studied by fast perfusion in Xenopus laevis oocytes. This compound has previously been shown to potentiate glycine responses in rat spinal neurons between 10 nM and 1 μM, independently of its 5-HT3 antagonist properties. In contrast, submicromolar concentrations of ICS-205,930 failed to affect responses of homomeric GlyRs formed from human α1 or α2 subunits, and micromolar concentrations (1{\textendash}20 μM) acted differentially on the two types of homomeric receptors, potentiating the responses to glycine (10{\textendash}20 μM) of α1 homomeric GlyRs and inhibiting the responses of α2 homomeric GlyRs. GlyRs β subunits markedly influenced the modulations induced by ICS-205,930. In oocytes expressing α1/β or α2/β heteromeric GlyRs, low concentrations of ICS-205,930 (20 nM{\textendash}1 μM) induced a potentiation of glycine responses that was counteracted by an inhibitory effect at higher concentrations. Thus, GlyRs β subunits reduce by 2 orders of magnitude the concentration range potentiating α1-containing GlyRs and are required for potentiation of α2-containing GlyRs. These results reveal a new high-affinity potentiating site on GlyRs, to which β subunits participate. The difference in ICS sensitivity between α1 and α2 GlyRs cannot be explained by their difference in TM2 segment and extracellular domains partly conserved between glycine and 5-HT3 receptors are probably involved in the interaction of some 5-HT3antagonists with GlyRs.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/58/4/763}, eprint = {https://molpharm.aspetjournals.org/content/58/4/763.full.pdf}, journal = {Molecular Pharmacology} }