Bicuculline antagonizes 5-HT3A and α2 glycine receptors expressed in Xenopus oocytes

The present study examined the effects of bicuculline on the mouse 5-hydroxytryptamine(3A) receptor (5-HT3A receptor and the human alpha 2 subunit of the glycine receptor. Bicuculline antagonized both the 5-HT3A receptor (IC50 = 20.12 +/- 0.39 mu M) and the alpha 2 glycine receptor (IC50 = 169.40 +/- 1.73 mu M). A competitive form of antagonism by bicuculline was suggested by experiments in which the EC(50)s for 5-HT and glycine were increased in the 5-HT3A and alpha 2 glycine receptors, respectively, as bicuculline concentrations were increased. A competitive nature of antagonism by bicuculline at the 5-HT3A receptor was also suggested by displacement of the competitive antagonist, [H-3]GR65630 in SF21 insect cells expressing the 5-HT3A receptor (K-i = 19.01 +/- 0.71 mu M). Our data and that of others reveal that bicuculline, a purported selective antagonist of the GABA(A) receptor, antagonizes at least one receptor subclass in every member of the superfamily of ligand-gated ion channels. (C) 2000 Elsevier Science B.V. All rights reserved.