Opposing effects of different steroid sulfates on GABAA receptor-mediated chloride uptake

Brain Res. 1998 Apr 20;790(1-2):334-8. doi: 10.1016/s0006-8993(98)00145-0.


Steroids with the 3alpha-hydroxy-5alpha- or 5beta-reduced configurations of the A ring interact with the gamma-aminobutyric acid (GABA) type A receptor chloride channel complex and potentiate the stimulation of Cl- uptake by GABA agonists. Conversely, the sulfate esters of 3beta-hydroxy-5-ene neurosteroids pregnenolone and dehydroepiandrosterone behave as inhibitory modulators. In the present work, steroid sulfates were tested for their ability to modulate muscimol-induced chloride ion uptake into cortical synaptoneurosomes. 3alpha-Hydroxy-5alpha-pregnan-20-one sulfate and several other 3alpha-hydroxy-steroid sulfates potentiated, whereas 3beta-hydroxy-steroid sulfates inhibited muscimol effect. It is concluded that GABA-agonistic or antagonistic properties of steroid sulfates depend on the alpha or beta orientation of the sulfate moiety linked to the A ring.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Chlorides / pharmacokinetics*
  • Dehydroepiandrosterone Sulfate / pharmacology
  • GABA Agonists / pharmacology
  • GABA Modulators / pharmacology
  • GABA-A Receptor Agonists*
  • In Vitro Techniques
  • Ionophores / pharmacology
  • Male
  • Muscimol / pharmacology
  • Pregnanolone / pharmacology
  • Pregnenolone / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism


  • Chlorides
  • GABA Agonists
  • GABA Modulators
  • GABA-A Receptor Agonists
  • Ionophores
  • Receptors, GABA-A
  • pregnenolone sulfate
  • Muscimol
  • Dehydroepiandrosterone Sulfate
  • Pregnenolone
  • Pregnanolone