Agonist discrimination between AMPA receptor subtypes

T Coquelle; J K Christensen; T G Banke; U Madsen; A Schousboe; Darryl Pickering

Agonist discrimination between AMPA receptor subtypes

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

35 Citations (Scopus)

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.

Original language	English
Journal	NeuroReport
Volume	11
Issue number	12
Pages (from-to)	2643-8
Number of pages	5
ISSN	0959-4965
Publication status	Published - 2000

Cite this

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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.",

author = "T Coquelle and Christensen, {J K} and Banke, {T G} and U Madsen and A Schousboe and Darryl Pickering",

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",

year = "2000",

language = "English",

volume = "11",

pages = "2643--8",

journal = "NeuroReport",

issn = "0959-4965",

publisher = "Lippincott Williams & Wilkins",

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TY - JOUR

T1 - Agonist discrimination between AMPA receptor subtypes

AU - Coquelle, T

AU - Christensen, J K

AU - Banke, T G

AU - Madsen, U

AU - Schousboe, A

AU - Pickering, Darryl

N1 - 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

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 10976936

SN - 0959-4965

VL - 11

SP - 2643

EP - 2648

JO - NeuroReport

JF - NeuroReport

IS - 12

ER -

Agonist discrimination between AMPA receptor subtypes

Abstract

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