Agonist discrimination between AMPA receptor subtypes.
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.
Coquelle
T
T
Neuroscience PharmaBiotec Research Center, Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen.
Christensen
J K
JK
Banke
T G
TG
Madsen
U
U
Schousboe
A
A
Pickering
D S
DS
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
D007473:Ion Channels; D020033:Protein Isoforms; D018091:Receptors, AMPA; D011994:Recombinant Proteins; C023366:4-bromohomoibotenic acid; D007051:Ibotenic Acid