Steroid Hormone Metabolites Are Barbiturate-Like Modulators of the GABA Receptor

American Association for the Advancement of Science (AAAS) - Tập 232 Số 4753 - Trang 1004-1007 - 1986
Monika Majewska1, Neil L. Harrison2, Rochelle D. Schwartz1, Jeffery L. Barker2, Steven M. Paul1
1Sections on Molecular Pharmacology and Preclinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892.
2Laboratory of Neurophysiology, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Tóm tắt

Two metabolites of the steroid hormones progesterone and deoxycorticosterone, 3α-hydroxy-5α-dihydroprogesterone and 3α,5α-tetrahydrodeoxycorticosterone, are potent barbiturate-like ligands of the γ-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 36 Cl - ) 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.

Từ khóa


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American Association for the Advancement of Science (AAAS)

Tập 232 Số 4753

1004-1007

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