Agonist discrimination between AMPA receptor subtypes

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
Issue number12
Pages (from-to)2643-8
Number of pages5
Publication statusPublished - 2000

Bibliographical note

Keywords: Animals; Binding, Competitive; Cell Line; Dose-Response Relationship, Drug; Female; Ibotenic Acid; Insects; Ion Channels; Oocytes; Protein Isoforms; Receptors, AMPA; Recombinant Proteins; Xenopus laevis

ID: 20122739