GABA-dependent modulation of the Cl- ionophore by steroids in rat brain

Kelvin W. Gee, Wen Chung Chang, Roberta E. Brinton, Bruce S. McEwen

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

Steroids inhibit the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to the GABAA-benzodiazepine receptor (GBR) linked Cl- ionophore in a GABA dependent manner but not through the GABAA receptor. The most potent steroid evaluated is a naturally occuring metabolite of progesterone, 3 α-hydroxy,5 α-dihydroprogesterone with an IC50 of ≈ 17 nM. Structural requirements necessary for inhibitory activity coincide with those reported for anticonvulsant and anesthetic actions. Coupled with earlier evidence that these steroids do not act directly at the benzodiazepine receptor nor the [35S]TBPS labeled site to modulate the Cl- ionophore, the possibility is proposed that a distinct membrane-bound 'steroid site' coupled to the GBR-Cl- ionophore complex exists.

Original languageEnglish (US)
Pages (from-to)419-423
Number of pages5
JournalEuropean Journal of Pharmacology
Volume136
Issue number3
DOIs
StatePublished - Apr 29 1987
Externally publishedYes

Keywords

  • Anesthetics
  • Anticonvulsants
  • Chloride channels
  • GABA
  • Progesterone
  • Steroids

ASJC Scopus subject areas

  • Pharmacology

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