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  • 1
    Publication Date: 1986-05-23
    Description: Two metabolites of the steroid hormones progesterone and deoxycorticosterone, 3 alpha-hydroxy-5 alpha-dihydroprogesterone and 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone, are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex. At concentrations between 10(-7) and 10(-5)M both steroids inhibited binding of the convulsant t-butylbicyclophosphorothionate to the GABA-receptor complex and increased the binding of the benzodiazepine flunitrazepam; they also stimulated chloride uptake (as measured by uptake of 36Cl-) into isolated brain vesicles, and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons. These data may explain the ability of certain steroid hormones to rapidly alter neuronal excitability and may provide a mechanism for the anesthetic and hypnotic actions of naturally occurring and synthetic anesthetic steroids.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Majewska, M D -- Harrison, N L -- Schwartz, R D -- Barker, J L -- Paul, S M -- New York, N.Y. -- Science. 1986 May 23;232(4753):1004-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: 20-alpha-Dihydroprogesterone/*analogs & derivatives/metabolism/pharmacology ; Animals ; Bicyclo Compounds/metabolism ; *Bicyclo Compounds, Heterocyclic ; Binding, Competitive ; Brain/metabolism ; Cells, Cultured ; Chlorides/metabolism ; Desoxycorticosterone/*analogs & derivatives/metabolism/pharmacology ; Drug Synergism ; Flunitrazepam/metabolism ; Hippocampus/metabolism ; In Vitro Techniques ; Ion Channels/metabolism ; Progesterone/*analogs & derivatives/metabolism/pharmacology ; Rats ; Receptors, GABA-A/*drug effects/metabolism ; Spinal Cord/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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