Neurosteroids stimulate G protein-coupled sigma receptors in mouse brain synaptic membrane

Dehydroepiandrosterone, its sulfate (DHEAS) and pregnenolone sulfate, repre sentative neurosteroids as well as (+)-pentazocine concentration-dependentl y stimulated the [S-35]GTP gammaS binding in synaptic membranes of mouse pr efrontal cortex. These stimulations were blocked by NE-100, a sigma-recepto r antagonist, and by progesterone, another type of neurosteroid. The DHEAS- induced stimulation was blocked by the pertussis toxin (PTX)-treatment, and completely recovered by reconstitution of PTX-treated membranes with recom binant G(i1), but not with G(oA). DHEAS also stimulated the [S-35]GTP gamma S binding in the coronal sections of mouse brain in NE-100- or progesterone -reversible manner. These findings suggest that some neurosteroids may act on metabotropic sigma receptors, and this study may be the first to show th e coupling of neurosteroid binding site and G(i). (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.