Agonist discrimination between AMPA receptor subtypes.

T Coquelle, J K Christensen, T G Banke, U Madsen, A Schousboe, D S Pickering

Index: Neuroreport 11(12) , 2643-8, (2000)

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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.