The effect of dehydroepiandrosterone sulfate and allopregnanolone sulfate on the binding of [(3)H]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 [(3)H]ifenprodil binding at 10, 30 or 100 nM, 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.
Johansson
Tobias
T
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, P.O. Box 591, S-75124 Uppsala, Sweden. Tobias.Johansson@farmbio.uu.se
Le Grevès
Pierre
P
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D005625:Frontal Lobe / Q000378:metabolism*; D007700:Kinetics; D010880:Piperidines / Q000493:pharmacokinetics*; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D019314:Dehydroepiandrosterone Sulfate; D011280:Pregnanolone; C010739:ifenprodil