PT - JOURNAL ARTICLE AU - Geoffrey T. Swanson AU - Tim Green AU - Stephen F. Heinemann TI - Kainate Receptors Exhibit Differential Sensitivities to (<em>S</em>)-5-Iodowillardiine DP - 1998 May 01 TA - Molecular Pharmacology PG - 942--949 VI - 53 IP - 5 4099 - http://molpharm.aspetjournals.org/content/53/5/942.short 4100 - http://molpharm.aspetjournals.org/content/53/5/942.full SO - Mol Pharmacol1998 May 01; 53 AB - Characterization of the role of kainate receptors in excitatory synaptic transmission has been hampered by a lack of subtype-selective pharmacological agents. (S)-5-Iodowillardiine (IW), an analog of willardiine [(S)-1-(2-amino-2-carboxyethyl)pyrimidine-2,4-dione], a heterocyclic amino acid found in Acacia andMimosa seeds, was previously shown to be highly potent on native kainate receptors in dorsal root ganglion neurons. We examined the responses evoked by IW from recombinant homomeric and heteromeric kainate receptors expressed in human embryonic kidney 293 cells. IW potently elicited currents from glutamate receptor 5 (GluR5)-expressing cells, but showed no activity on homomeric GluR6 or GluR7 receptors. Co-expression of these receptor subunits with KA-2 subunits produced receptors that were weakly sensitive to IW. GluR5/KA-2 receptors had a higher EC50 value than homomeric GluR5 and exhibited a much faster recovery from desensitization. Finally, we found that the IW selectivity for GluR5 compared with GluR6 was determined by amino acid 721, which was previously shown to control α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate sensitivity of these kainate receptor subunits. The pharmacological selectivity and commercial availability of IW suggests that this compound may be of use in characterizing the molecular constituents of native kainate receptor responses. The American Society for Pharmacology and Experimental Therapeutics