TitleSTEROID MODULATION OF GABA(A) RECEPTORS IN AN AMPHIBIAN BRAIN
Publication TypeJournal Article
Year of Publication1994
AuthorsOrchinik, M, Murray, TF, Moore, FL
JournalBrain Research
Volume646
Pagination258-266
Type of ArticleJournal Article
ISSN0006-8993
Abstract

Steroids can modulate gamma-aminobutyric acid (GABA(A)) 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 GABA(A) receptors in amphibian brain tissue. Equilibrium binding parameters for t-butylbicyclophosphorothionate ([S-35]TBPS) and [H-3]flunitrazepam were similar in Taricha granulosa and mammalian brains, as was the allosteric regulation of [S-35]TBPS and [H-3]flunitrazepam binding by GABA. The rank order and absolute potencies of steroids to inhibit [S-35]TBPS binding and enhance [H-3]flunitrazepam binding were also similar in Taricha and rat brains. As in mammalian studies, physiological concentrations of corticosterone had no effect on ligand binding or GABA-stimulated C1(-) uptake. In autoradiographic studies, 3 alpha-hydroxy-5 alpha-pregnan-20-one inhibited [S-35]TBPS binding sites in all brain regions examined, whereas corticosterone had no effect on [S-35]TBPS binding. These studies suggest that the steroid recognition sites an GABA(A) receptors have been highly conserved through vertebrate evolution and thus portend physiologically important functions. However, the pharmacological profiles for the GABA(A) receptor and the high-affinity corticosteroid receptor are apparently different, suggesting there are multiple types of steroid recognition sites on neuronal membranes.

URL<Go to ISI>://WOS:A1994NM41600012
DOI10.1016/0006-8993(94)90087-6