Estrogen mediated inhibition of dopamine transport in the striatum: regulation by G alpha i/o.
In the current study, the interaction between estrogen priming and dopamine D2 receptor activation on dopamine uptake in the striatum of ovariectomized female rats was investigated. Basal ADP-[(32)P(i)]ribosylation of G(i/o) was examined in synaptosomal membranes prepared from ovariectomized, estrogen primed or N-p-(isothiocyanatophenethyl) spiperone (NIPS) treated rats. [(32)P(i)]-incorporation was significantly increased (141%) in tissue from NIPS treated animals but attenuated (57%) in tissue from estrogen primed animals. Dopamine uptake kinetics were measured in vivo following manipulation of the heterotrimeric G-protein by pertussis toxin (0.5 microg, 48 h). Pertussis toxin significantly inhibited dopamine uptake at all concentrations of dopamine examined. Co-treatment with estrogen and pertussis toxin resulted in a further attenuation of dopamine transport at high but not low dopamine concentrations. These data are consistent with an estrogen mediated alteration of G-protein activity and support the hypothesis that estrogen may alter transporter activity through a modulation of dopamine D2 autoreceptor/G alpha(i/o) protein coupling.
Thompson
Tina L
TL
Division of Basic Science, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207, USA. thompson_tl@mercer.edu
Certain
Matthew E
ME
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D010052:Ovariectomy; D037342:Pertussis Toxin / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013134:Spiperone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D010761:Phosphorus Radioisotopes; C068824:N-(4-isothiocyanatophenethyl)spiperone; D000246:Adenosine Diphosphate Ribose; D013134:Spiperone; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D004298:Dopamine