Distinct effect of pregnenolone sulfate on NMDA receptor subtypes

Citation
M. Ceccon et al., Distinct effect of pregnenolone sulfate on NMDA receptor subtypes, NEUROPHARM, 40(4), 2001, pp. 491-500
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROPHARMACOLOGY
ISSN journal
0028-3908 → ACNP
Volume
40
Issue
4
Year of publication
2001
Pages
491 - 500
Database
ISI
SICI code
0028-3908(200103)40:4<491:DEOPSO>2.0.ZU;2-U
Abstract
Using rapid agonist applications to transfected HEK-293 cells, we investiga ted pregnenolone sulfate (PS) effects on deactivation and desensitization o f recombinant NMDA receptors subtypes. PS prolonged the deactivation of res ponses produced by brief applications of L-glutamate with all subunit combi nations tested. The action of PS was larger on NR1a/NR2A than on NR1a/NR2B channels. PS slowed the rate of macroscopic desensitization of the response s with all subunit combinations tested. In contrast, PS had little effect o n current rise time and had much reduced action on responses with L-cysteat e, a low affinity agonist. Our results suggest that PS decreases agonist unbinding. However, this acti on is counteracted by decreased desensitization. Since desensitization prod uces slow deactivating components, particularly with NR1a/NR2B receptors, t his underlies the decreased PS effect with these subtypes. Indeed PS action was mainly observed on the fast component of deactivation. Furthermore, pr olongation of NR1a/NR2A responses was similar to that of responses from NR1 b/NR2B receptor, a subtype characterized by reduced desensitization. PS prolongation of evoked NMDA receptor mediated synaptic currents from cor tical neuronal primary culture(s) was not significantly different from that of responses with NR1a/NR2B receptors indicating that native receptors in these neurons comprised at least some heteromeric combinations of these two subunits. (C) 2001 Elsevier Science Ltd. All rights reserved.