Pii: S0304-3940(00)00868-5

نویسندگان

  • Hideo Mukai
  • Shigeo Uchino
  • Suguru Kawato
چکیده

Pregnenolone sulfate (PREGS) potentiates the N-methyl-d-aspartate (NMDA) receptor-mediated Ca-signals in cultured hippocampal neurons. The NMDA receptor family has several different subunits whose expression in neurons has distinct spatial and temporal patterns. To examine subunit speci®city of the PREGS action, we have investigated the effect of PREGS on recombinant GluR 12/z1 (NR2B/NR1) type NMDA receptors stably expressed in Chinese hamster ovary cells using heat shock promoters. PREGS enhanced the Ca in ̄ux through the GluR 12/z1 receptors in a dosedependent manner. The EC50 of PREGS for the GluR 12/z1 receptors was 8.6 mM. Other sulfated neurosteroids, dehydroepiandrosterone sulfate (DHEAS), 17b-estradiol sulfate and 3a-ol-5b-pregnan-20-one sulfate (3a5bS), inhibited the positive modulatory effect of PREGS on the GluR 12/z1 NMDA receptors. Ifenprodil, a speci®c inhibitor of GluR 12 subunit, abolished the NMDA-induced Ca in ̄ux even in the presence of PREGS. These results imply that PREGS positively modulates the Ca in ̄ux through the GluR 12/z1 receptors which are expressed from the embryonic period. q 2000 Elsevier Science Ireland Ltd. All rights reserved.

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تاریخ انتشار 2000