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The Selective Interaction of Neurosteroids with the GABAA Receptor

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Neurosteroids

Part of the book series: Contemporary Endocrinology ((COE,volume 16))

Abstract

Some endogenous pregnane steroids have long been known to produce rapid sedative and anesthetic effects (1). The speed of onset of these behavioral effects precludes a genomic mechanism of action for such steroids, but it was not until Harrison and Simmonds (2)demonstrated that a synthetic steroidal anesthetic, alphaxalone (3α-hydroxy-5α-pregnane-11,20-dione), selectively enhanced the interaction of GABA with the GABAA receptor, that a logical mechanism to explain the behavioral effects of these compounds emerged. GABA acting via the GABAA receptor mediates much of the “fast” inhibitory synaptic transmission in the mammalian brain (3).The GABAA receptor is a member of the cysteine-cysteine loop transmitter-gated ion channel family that includes glycine, nicotinic, and 5-HT3 receptors (4).Upon activation by GABA, the associated chloride selective ion channel is opened that increases neuronal membrane conductance and effectively shunts the influence of excitatory transmitters such as glutamate (3).

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  1. Jeremy J. Lambert MD
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  2. Delia Belelli MD
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  4. Marco Pistis MD
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  1. Institut National de la Santé et de la Recherche Médicale, Collége de France, Le Kremlin-Bicêtre, France

    Etienne-Emile Baulieu MD, PhD , Paul Robel MD, PhD  & Michael Schumacher PhD ,  & 

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Lambert, J.J., Belelli, D., Shepherd, S.E., Pistis, M., Peters, J.A. (1999). The Selective Interaction of Neurosteroids with the GABAA Receptor. In: Baulieu, EE., Robel, P., Schumacher, M. (eds) Neurosteroids. Contemporary Endocrinology, vol 16. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-693-5_7

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