Pregnenolone-sulfate: an endogenous antagonist of the gamma-aminobutyric acid receptor complex in brain?

Journal Article (Journal Article)

The interaction of the 'neurosteroid', pregnenolone-sulfate (PS), with the GABA/benzodiazepine/chloride ionophore receptor complex was investigated in rat brain subcellular preparations. At low micromolar concentrations PS competitively inhibited the binding of the convulsant [35S]t-butylbicyclophosphorothionate (TBPS) and antagonized pentobarbital-stimulated [3H]flunitrazepam binding to synaptosomes. In addition, PS inhibited muscimol-stimulated 36Cl-uptake in brain synaptoneurosomes, including that PS has characteristics of a relatively potent antagonist of the chloride channel coupled to the GABA receptor. Together with our previous finding that A-ring reduced metabolites of progesterone and deoxycorticosterone also interact with the GABA receptor complex but as hypnotic barbiturates, these data suggest that the regulation of GABAergic neurotransmission by various neurosteroids may be an important mechanism for controlling neuronal excitability.

Full Text

Duke Authors

Cited Authors

  • Majewska, MD; Schwartz, RD

Published Date

  • February 24, 1987

Published In

Volume / Issue

  • 404 / 1-2

Start / End Page

  • 355 - 360

PubMed ID

  • 3032339

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/0006-8993(87)91394-1


  • eng

Conference Location

  • Netherlands