The effect of dehydroepiandrosterone sulfate and allopregnanolone sulfate on the binding of [3H]ifenprodil to the N-methyl-D-aspartate receptor in rat frontal cortex membrane

Neurosteroids have been shown to modulate the N-methyl-D-aspartate (NMDA) receptor function. Dehydroepiandrosterone sulfate (DHEAS) is shown to participate in memory and learning processes as well as preventing glutamate neurotoxicity in hippocampus. In this study we have focused on the modulatory effect of neurosteroids on ifenprodil binding to the NR2B subunit of the NMDA receptor. We show that DHEAS and allopregnanolone sulfate (ALLOPREGS) exert different effects on the [H-3]ifenprodil binding at 10, 30 or 100nM, corresponding to physiological concentrations. The effects include changes in the ifenprodil displacement curve, changing it from a one-site fit into a two-site fit leaving B-max, K-d and K-off unaffected. Our results indicate that DHEAS and ALLOPREGS induce an allosteric modulation of the NMDA receptor, an observation that might contribute to the understanding of the effects of these neurosteroids. (c) 2005 Elsevier Ltd. All rights reserved.