Neuroreport 2000-08-21

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)

Full Text: HTML

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.

Related Compounds

  • (RS)-1-(3-FLUOR...

Related Articles:

Turning behaviour and catalepsy after injection of excitatory amino acids into rat substantia nigra.

1981-05-29

[Neurosci. Lett. 23 , 337, (1981)]

Excitatory amino acid agonists. Enzymic resolution, X-ray structure, and enantioselective activities of (R)- and (S)-bromohomoibotenic acid.

1989-10-01

[J. Med. Chem. 32(10) , 2254-60, (1989)]

Structural determinants of agonist-specific kinetics at the ionotropic glutamate receptor 2.

2005-08-23

[Proc. Natl. Acad. Sci. U. S. A. 102(34) , 12053-8, (2005)]

Identification of amino acid residues in GluR1 responsible for ligand binding and desensitization.

2001-05-01

[J. Neurosci. 21(9) , 3052-62, (2001)]

4-Methylhomoibotenic acid activates a novel metabotropic glutamate receptor coupled to phosphoinositide hydrolysis.

1997-11-01

[J. Pharmacol. Exp. Ther. 283(2) , 742-9, (1997)]

More Articles...