TY - JOUR T1 - Effects of bromowillardiine and willardiine on non-N-methyl-D-aspartate receptors in postnatal rat hippocampal neurons. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 45 LP - 51 VL - 40 IS - 1 AU - C F Zorumski AU - L L Thio AU - D B Clifford Y1 - 1991/07/01 UR - http://molpharm.aspetjournals.org/content/40/1/45.abstract N2 - The physiology and pharmacology of willardiine and bromowillardiine, structural analogues of quisqualate, were studied in cultured postnatal rat hippocampal neurons using whole-cell voltage-clamp techniques. These agonists appear to act at a shared non-N-methyl-D-aspartate (non-NMDA) receptor-channel complex and gate nonselective cationic currents. Willardiine currents desensitize rapidly and to a much greater degree than bromowillardiine currents. In addition, the brominated compound produces steady state currents that are 5 times larger than those produced by willardiine at saturation. Bromowillardiine is also a more efficacious excitotoxin, producing about 3-fold greater acute neuronal damage than willardiine at saturating concentrations. These results suggest that agonist structure affects the ability of non-NMDA agonists to induce desensitization and add support to the hypothesis that receptor desensitization serves to limit acute excitotoxicity in cultured neurons. ER -