Neurosteroids stimulate G protein-coupled sigma receptors in mouse brain synaptic membrane.
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).
Ueda
H
H
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, 852-8521, Nagasaki, Japan. ueda@net.nagasaki-u.ac.jp
Yoshida
A
A
Tokuyama
S
S
Mizuno
K
K
Maruo
J
J
Matsuno
K
K
Mita
S
S
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000493:pharmacokinetics; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D011374:Progesterone / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D013256:Steroids / Q000378:metabolism / Q000493:pharmacokinetics*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000701:Analgesics, Opioid; D000840:Anisoles; D014150:Antipsychotic Agents; D011437:Propylamines; D017480:Receptors, sigma; D011994:Recombinant Proteins; D013256:Steroids; D010566:Virulence Factors, Bordetella; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins