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

Neurosci Res. 2001 Sep;41(1):33-40. doi: 10.1016/s0168-0102(01)00258-9.

Abstract

Dehydroepiandrosterone, its sulfate (DHEAS) and pregnenolone sulfate, representative neurosteroids as well as (+)-pentazocine concentration-dependently stimulated the [35S]GTPgammaS binding in synaptic membranes of mouse prefrontal cortex. These stimulations were blocked by NE-100, a sigma-receptor 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 recombinant G(i1), but not with G(oA). DHEAS also stimulated the [35S]GTPgammaS 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 the coupling of neurosteroid binding site and G(i).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Anisoles / pharmacology
  • Antipsychotic Agents / pharmacology
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Brain / drug effects*
  • Brain / metabolism
  • Dehydroepiandrosterone Sulfate / pharmacokinetics
  • GTP-Binding Proteins / drug effects*
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / pharmacology
  • Male
  • Mice
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pertussis Toxin
  • Progesterone / pharmacology
  • Propylamines / pharmacology
  • Radioligand Assay
  • Receptors, sigma / drug effects*
  • Receptors, sigma / metabolism
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Steroids / metabolism
  • Steroids / pharmacokinetics*
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Synaptic Membranes / drug effects*
  • Synaptic Membranes / metabolism
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Analgesics, Opioid
  • Anisoles
  • Antipsychotic Agents
  • Propylamines
  • Receptors, sigma
  • Recombinant Proteins
  • Steroids
  • Virulence Factors, Bordetella
  • N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
  • Progesterone
  • Dehydroepiandrosterone Sulfate
  • Pertussis Toxin
  • GTP-Binding Proteins