Bicuculline antagonizes 5-HT(3A) and alpha2 glycine receptors expressed in Xenopus oocytes.
The present study examined the effects of bicuculline on the mouse 5-hydroxytryptamine(3A) receptor (5-HT(3A) receptor and the human alpha2 subunit of the glycine receptor. Bicuculline antagonized both the 5-HT(3A) receptor (IC(50)=20.12+/-0.39 microM) and the alpha2 glycine receptor (IC(50)=169.40+/-1.73 microM). 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-HT(3A) and alpha2 glycine receptors, respectively, as bicuculline concentrations were increased. A competitive nature of antagonism by bicuculline at the 5-HT(3A) receptor was also suggested by displacement of the competitive antagonist, [3H]GR65630 in SF21 insect cells expressing the 5-HT(3A) receptor (K(i)=19.01+/-0.71 microM). 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.
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Department of Pharmacology, Texas Tech University Health Sciences Center, 3601 Fourth Street, Lubbock, USA.
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D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D001667:Binding, Competitive; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D011869:Radioligand Assay; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014982:Xenopus laevis
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018009:Receptors, Glycine; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D001640:Bicuculline