In vitro effects of 17 beta-oestradiol on the sensitivity of receptors coupled to adenylate cyclase on striatal neurons in primary culture.
Pretreatment of intact striatal neurons from the mouse embryo in primary culture with 17 beta-oestradiol (10(-9) M), 24 hours) enhanced the stimulation of adenylate cyclase activity induced by either dopamine (D1 receptors), isoproterenol, serotonin or 2-chloroadenosine (maximal effective concentrations) but suppressed inhibitory responses evoked by agonists of D2-dopaminergic or enkephalin (mu and delta) receptors. Binding studies indicated that some of these effects are (beta 1) or are not (D1 and D2) associated with changes in the number of receptors. Similar effects were partially seen with testosterone but not with 17 alpha-oestradiol, progesterone or dexamethasone and those induced by 17 beta-oestradiol were abolished when cells were exposed to inhibitors of mRNA transcription (alpha-amanitin) or protein synthesis (cycloheximide). Modifications in the properties of Gs or Go,i proteins were postulated because the number of adenylate cyclase catalytic subunits was not affected by 17 beta-oestradiol pretreatment. Results of ADP-ribosylation experiments with cholera toxin or pertussis toxin and of immunoblot experiments with anti-G alpha o and anti-G beta sera led us to suggest that 17 beta-oestradiol induces qualitative modifications in Go,i proteins leading to a stabilization of the associated form of the heterotrimer G alpha o,i beta gamma. In fact, pretreatment with pertussis toxin (which impairs G alpha o,i beta gamma dissociation) mimics the effects of 17 beta-oestradiol on responses of adenylate cyclase to stimulatory and inhibitory agonists.
Maus
M
M
Laboratoire de Neuropharmacologie, INSERM U 114, Collège de France, Paris.
Prémont
J
J
Glowinski
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D011954:Receptors, Dopamine / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism
D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D004958:Estradiol; D000262:Adenylyl Cyclases