Journal of Neurochemisiry Raven Press, Ltd., New York 0 1991 International Society for Neurochemistry
Rapid Communication
Differential Responses of Expressed Recombinant Human y-Aminobutyric AcidAReceptors to Neurosteroids Nancy C. Lan, Kelvin W. Gee, *Michael B. Bolger, and Jie Sheng Chen Departments of Molecular Pharmacology and Toxicology and *Pharmaceutical Sciences, School of Pharmacy, University of Southern California,Los Angeles, California, U.S.A.
Abstract Neuroactive steroids, in particular 3a-hydroxypregnanes, are allosteric modulators of the y-aminobutyric acid, (GABA,) receptor. Regionally selective expression of receptor subunit subtypes may account for differential responsiveness of tissues to GABAergic inhibition and neurosteroid modulatory effects. The effect of 5apregnan-3a-ol-20-one (epiallopregnanolone)on heterotropic cooperativity on the GABAAreceptor complex has been studied in three subtypesof expressed recombinant human receptors and in rat brain and spinal cord. Steroid potentiation of [3H]flunitrazepambinding was greatest for the ( ~ j f l I y 2receptor complex, whereas al&yt and a2&yzcomplexesshowed
Rapid Communication
Differential Responses of Expressed Recombinant Human y-Aminobutyric AcidAReceptors to Neurosteroids Nancy C. Lan, Kelvin W. Gee, *Michael B. Bolger, and Jie Sheng Chen Departments of Molecular Pharmacology and Toxicology and *Pharmaceutical Sciences, School of Pharmacy, University of Southern California,Los Angeles, California, U.S.A.
Abstract Neuroactive steroids, in particular 3a-hydroxypregnanes, are allosteric modulators of the y-aminobutyric acid, (GABA,) receptor. Regionally selective expression of receptor subunit subtypes may account for differential responsiveness of tissues to GABAergic inhibition and neurosteroid modulatory effects. The effect of 5apregnan-3a-ol-20-one (epiallopregnanolone)on heterotropic cooperativity on the GABAAreceptor complex has been studied in three subtypesof expressed recombinant human receptors and in rat brain and spinal cord. Steroid potentiation of [3H]flunitrazepambinding was greatest for the ( ~ j f l I y 2receptor complex, whereas al&yt and a2&yzcomplexesshowed
