Steroid modulation of GABA_A receptors in an amphibian brain

Steroids can modulate γ-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 ([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 GABA_A receptors bave been highly conserved through vertebrate evolution and thus portend physiologically important functions. However, the pharmacological profiles for the GABA_A receptor and high-affinity coritcosteroid receptor are apparently different, suggesting there are multiple types of steroid recognition sites on neuronal membranes.