title: Agonist discrimination between AMPA receptor subtypes.
abstract: The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H]AMPA radioligand binding experiments. (S)-4-bromohomoibotenic acid (BrHIBO) exhibited a 126-fold selectivity for GluR1o compared to GluR3o. Xenopus laevis oocytes were used to express functional homomeric and heteromeric recombinant AMPA-R and to determine BrHIBO potency (EC50) at these channels. (R,S)-BrHIBO exhibited a 37-fold selectivity range amongst the AMPA-R. It is hoped that BrHIBO can be used as a lead structure for the development of other subtype-selective compounds.
authors.affiliation: Neuroscience PharmaBiotec Research Center, Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen.
authors.forename: T
authors.initials: T
authors.lastname: Coquelle
authors.forename: J K
authors.initials: JK
authors.lastname: Christensen
authors.forename: T G
authors.initials: TG
authors.lastname: Banke
authors.forename: U
authors.initials: U
authors.lastname: Madsen
authors.forename: A
authors.initials: A
authors.lastname: Schousboe
authors.forename: D S
authors.initials: DS
authors.lastname: Pickering
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007313:Insecta / Q000166:cytology; D007473:Ion Channels / Q000378:metabolism; D009865:Oocytes; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D007473:Ion Channels; D020033:Protein Isoforms; D018091:Receptors, AMPA; D011994:Recombinant Proteins; C023366:4-bromohomoibotenic acid; D007051:Ibotenic Acid