Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular Ca2+ in cultured rat hippocampal neurons

Robert P. Irwin, Nicholas J. Maragakis, Michael A Rogawski, Robert H. Purdy, David H. Farb, Steven M. Paul

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-d-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250 μM) caused a concentration-dependent and reversible potentiation of the rise (up to ∼ 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that occurs when hippocampal neurons are depolarized by high K+ in the presence of the NMDA receptor antagonist CPP. These data suggest that the previously reported excitatory properties of pregnenolone sulfate may be due, in part, to an augmentation of the action of glutamic acid at the NMDA receptor.

Original languageEnglish (US)
Pages (from-to)30-34
Number of pages5
JournalNeuroscience Letters
Issue number1
StatePublished - Jul 6 1992
Externally publishedYes


  • Intracellular Ca, Neuroactive steroid
  • NMDA receptor
  • Pregnenolone sulfate

ASJC Scopus subject areas

  • Neuroscience(all)


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