Steroid modulation of GABAA receptors in an amphibian brain

Miles Orchinik, Thomas F. Murray, Frank L. Moore

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Abstract

Steroids can modulate γ-aminobutyric acid (GABAA) receptor function in rat brains, but the physiological relevance of this mechanism is still unclear. To determine whether this phenomenon is widespread among vertebrates, we investigated steroid modulation of GABAA receptors in amphibian brain tissue. Equilibrium binding parameters for t-butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam were similar in Tricha glanulosa and mammalian brains, as was the allosteric regulation of [35S]TBPS and [3H]flunitrazepam binding in GABA. The rank order and absolute potencies of steroids to inhibit [35S]TBPS binding and enhance [3H]flunitrazepam binding were also similar in Taricha and rat brains. As in mammalian studies, physiological concentrations of corticosterone had no effect on ligand binding of GABA-stimulated Cl- uptake. In autoradiogrphic studies, 3α-hydroxy-5α-pregnan-20-one inhibited [35S]TBPS binding sites in all brain regions examined, whereas corticosterone had no effect on [35S]TBPS binding. These studies suggest that the steroid recognition sites on GABAA receptors bave been highly conserved through vertebrate evolution and thus portend physiologically important functions. However, the pharmacological profiles for the GABAA receptor and high-affinity coritcosteroid receptor are apparently different, suggesting there are multiple types of steroid recognition sites on neuronal membranes.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalBrain Research
Volume646
Issue number2
DOIs
StatePublished - May 23 1994
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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