TY - JOUR
T1 - Steroid modulation of GABAA receptors in an amphibian brain
AU - Orchinik, Miles
AU - Murray, Thomas F.
AU - Moore, Frank L.
N1 - Funding Information:
We would like to thank L. McKinney, M. Schroeder and Drs. J. Morgan, D. Booth, and P. Franklin for their assistance or expertise. This work was supported by NSF grants BNS-8901500 (F.L.M. and M.O.) and BNS-8909173 (F.L.M.). M.O. was supported by an NSF graduate fellowship.
PY - 1994/5/23
Y1 - 1994/5/23
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-8993(94)90087-6
DO - 10.1016/0006-8993(94)90087-6
M3 - Article
C2 - 8069672
AN - SCOPUS:0028176132
VL - 646
SP - 258
EP - 266
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -