Thyroid hormonal modulation of the binding and activity of the GABA(A) receptor complex of brain

J. V. Martin, D. B. Williams, R. M. Fitzgerald, H. K. Im, P. F. Vonvoigtlander

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Abstract

Thyroid hormones, which are known to act by genomic mechanisms in peripheral tissues, were found to influence the binding and function of the GABA(A) receptor complex in brain membranes. Submicromolar concentrations of triiodothyronine and thyroxine stereospecifically stimulated the binding of [35S]t-butylbicyclophosphorothionate (a convulsant ligand for the GABA(A) receptor complex) to highly washed rat brain membranes, while higher concentrations of the hormones inhibited radioligand binding. GABA-stimulated 36Cl- flux in isolated brain membrane sacs was inhibited by L- triiodothyronine with a half-maximally inhibitory concentration (IC50) of 10-7 M. Patch-clamp analysis of recombinant GABA(A) receptor subunits expressed in human embryonic kidney-293 cells showed an inhibition of chloride currents by thyroid hormones. This effect required only the α1β2 subunits, and was not blocked by the benzodiazepine antagonist flumazenil. Since thyroid hormones are known to he concentrated in nerve terminal preparations and subsequently released, the hormones may have non-genomic mechanisms of action as putative neurotransmitters or neuromodulators in brain and act through GABA(A) receptors.

Original languageEnglish (US)
Pages (from-to)705-713
Number of pages9
JournalNeuroscience
Volume73
Issue number3
DOIs
StatePublished - Aug 1996

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • GABA(A) receptor
  • chloride flux
  • human embryonic kidney (HEK-293) cells
  • neurosteroid
  • synaptosomes
  • t-butylbicyclophosphorothionate (TBPS)

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