Estrogen priming modulates autoreceptor-mediated potentiation of dopamine uptake.
The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.
Division of Basic Sciences, Mercer University School of Medicine, 1550 College St., 31207, Macon, GA, USA. thompson.t@gain.mercer.edu
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D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D017660:Autoreceptors / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D004298:Dopamine / Q000493:pharmacokinetics*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D010052:Ovariectomy; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D054645:Protein Phosphatase 1; D011714:Pyrans; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013141:Spiro Compounds; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000935:Antifungal Agents; D017660:Autoreceptors; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004791:Enzyme Inhibitors; D004967:Estrogens; D011714:Pyrans; D017447:Receptors, Dopamine D1; D013141:Spiro Compounds; C053079:tautomycin; D019257:Quinpirole; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D006220:Haloperidol; D004298:Dopamine