Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is a physiologically relevant modulator of GABA-ergic neurotransmission.

Article date: 1991/1/1

PubMed ID: 1667336

Journal name: Psychoneuroendocrinology (ISSN: 0306-4530)


3 alpha-Hydroxy-5 alpha-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABAA receptor binding, by determining the allosteric properties of HPO on the in vitro binding of 3H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of 3H-muscimol to GABAA receptor sites by 52% and enhanced the number of accessible binding sites from 5.5 +/- 0.5 to 7.5 +/- 1.3 pmol/mg protein at subnanomolar (0.1 nM) HPO concentrations. The modulatory effects of HPO on GABAA receptor binding provide evidence that this pregnane steroid might be a physiologically relevant modulator of GABAergic neurotransmission.

This document is available from: http://directlinks.cc/files/muscimol/1667336.pdf

Author List: Hiemke C, Jussofie A, Jüptner M

Publication Types: Journal Article

Substances mentioned in the article: Receptors, GABA-A; Tritium; Muscimol; Pregnanolone;

Mesh terms: Animals; Cell Membrane/metabolism; Cerebellum/metabolism; Dose-Response Relationship, Drug; Female; Muscimol/metabolism; Ovariectomy; Pregnanolone/physiology; Rats; Receptors, GABA-A/drug effects; Synaptic Transmission/drug effects; Tritium;

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